id: MODULE:viral_factory title: Viral factory (virus-induced replication microcompartment) description: >- A viral factory (VF) is a virus-induced intracellular microcompartment that concentrates the viral genome, the replication and transcription machinery, and the structural proteins of the progeny virion into one place, raising the local concentration of every reactant in the replication cycle while screening replication intermediates from host nucleic-acid sensors and nucleases. The module is deliberately mechanism-neutral at its core and taxon-spanning: what makes a VF a VF is the compartment boundary plus the co-localised replication, transcription, and assembly programme, not any one way of drawing the boundary. Three boundary mechanisms are modelled as variants along a single axis - a host-membrane-derived boundary (spherules, tubes, double-membrane vesicles, convoluted ER), a membraneless biomolecular condensate formed by liquid-liquid phase separation, and a self-assembled proteinaceous shell - because the same downstream programme runs inside all three. Around that core the module places the recruitment of host systems the factory depends on (cytoskeleton, mitochondria, donor membranes, host lipid kinases, in some lineages host transcription machinery), the shielding of replication intermediates from host defences, non-lytic egress, and the antagonists that act on the factory itself. status: DRAFT scope: ABSTRACT evidence: - source_id: PMID:42734359 title: The organization and dynamics of viral factories. statement: >- Source review for this module: defines viral factories as virus-induced microcompartments hosting genome replication, transcription, and virion assembly, and frames the membrane-bound / phase-separated / protein-shell diversity the module represents as a variant axis. supporting_text: >- Viral factories (VFs) are dynamic, virus-induced microcompartments that serve as centralized hubs in the host cell for viral genome replication, transcription, and virion assembly. - source_id: PMID:42734359 statement: >- Supports modelling the compartment boundary as a variant axis rather than as a fixed property of the module. supporting_text: >- Some are enclosed by host-derived membranes, while others exist as biomolecular condensates from liquid-liquid phase separation. - source_id: PMID:42734359 statement: >- Supports a distinct host-recruitment part alongside the viral replication programme. supporting_text: >- VFs recruit host lipids, cytoskeletal elements, and metabolic enzymes, effectively reprogramming the intracellular environment to favor viral replication. - source_id: GO:0039713 title: viral factory statement: >- Ontology grounding for the module as a whole. The GO definition already carries both halves of the module's boundary: replication efficiency and shielding from host defences. - source_id: PMID:24549844 title: Reovirus forms neo-organelles for progeny particle assembly within reorganized cell membranes. statement: >- Independent statement of the same three-part functional definition used here (concentration, defence evasion, coordinated release), from a dsRNA virus system. supporting_text: >- These highly specialized structures concentrate viral replication proteins and nucleic acids, prevent the activation of cell-intrinsic defenses, and coordinate the release of progeny particles. notes: >- Scope decisions. (1) The module is ABSTRACT: the boundary it draws is the factory itself, which recurs across RNA and DNA viruses of eukaryotes and across jumbo phages of bacteria, so most leaf roles are selectors with orienting representative members rather than a species-specific member list. Representative members are examples only; where a strain-specific reference entry exists it is cited, and representatives within one family descriptor may come from different reference strains. (2) Phage nuclei are included as a boundary variant, with a caveat. The source review is explicit that the chimallin-shelled compartments of Chimalliviridae are "not considered true VFs", and GO has no term for them. They are modelled here anyway because they satisfy the module's functional definition exactly - a boundary that concentrates replication and transcription, excludes translation, and blocks host nucleases - and because treating the boundary mechanism as the variant axis is the whole point of the module. The caveat is recorded on the variant node itself, not hidden here. (3) Translation is deliberately outside the module. In every system where it has been localised - mimivirus, and the phage nucleus - translation happens outside the factory, and that exclusion is a property worth stating rather than a part to include. (4) Host restriction factors and virophages are grouped as one optional "antagonists" part rather than scattered as negative regulation on individual steps, because both act on the assembled factory as a unit. (5) Provenance caution on the GO groundings. The GO viral-factory branch used throughout this module is not independent of ViralZone. Only GO:0039713 carries the dbxref VZ:1951, and it is the only term in the branch that the SPKW ViralZone audit scores (0.82 best-sentence similarity, its CLOSE_PARAPHRASE band). The children - spherule, double membrane vesicle, tube, virogenic stroma, peristromal region viral factory - carry no VZ dbxref, so they are outside that generated table; that their definitions also track the sections of VZ:1951 is this curator's reading on comparing the texts, not a measured result. GO does drop ViralZone's claim that filoviruses produce viroplasms. Citing VZ:1951 alongside those GO terms would therefore count one source twice rather than corroborate, so it is recorded here and not as an evidence item. The primary literature cited on each boundary variant is the independent support. knowledge_gaps: - gap_statement: >- No GO term denotes a proteinaceous (non-membrane, non-condensate) viral replication compartment such as the chimallin-bounded phage nucleus, and no term expresses the structural role of its shell subunits. boundary: >- The structure is solved and its principal component identified: the shell assembles primarily from chimallin (ChmA), which self-assembles into closed micrometre-scale compartments, and chimallin proteins carry only GO:0030430 host cell cytoplasm in UniProt. GO's viral-factory branch (GO:0039713 and descendants) is built entirely around eukaryotic host-cell compartments and has no prokaryotic-host member. GO does however already model proteinaceous bacterial compartments elsewhere: GO:0031469 bacterial microcompartment and GO:0140737 encapsulin nanocompartment are both is_a GO:0043232 intracellular membraneless organelle, and the shell of such a compartment is expressed as a molecular function (GO:0043886 structural constituent of carboxysome shell) rather than as a separate component term. The phage nucleus fits that established pattern; what is missing is the pair of terms, not the pattern. gap_kind: - ONTOLOGY - CURATION dark_aspect: CC_DARK status: OPEN significance: >- Without a term, the best-characterised example of viral compartmentalisation outside eukaryotes cannot be annotated at all, and the convergence between phage nuclei and eukaryotic viral factories - the comparison the source review is built around - is invisible to any GO-based analysis. resolution: >- Two terms following the carboxysome/encapsulin pattern: a cellular component for the phage nucleus under GO:0043232 intracellular membraneless organelle, and a molecular function for its shell subunits modelled on GO:0043886. Placing the compartment under the membraneless organelle branch rather than under GO:0039713 viral factory also avoids having to settle first whether the eukaryote-facing viral-factory branch should be generalised to prokaryotic hosts - though relating the two remains desirable, since the convergence is the biologically interesting claim. provenance: - reference_id: PMID:35922510 reference_section_type: ABSTRACT supporting_text: >- Here we find that the bacteriophage nuclear shell assembles primarily from one protein, which we name chimallin (ChmA). - reference_id: PMID:42734359 reference_section_type: DISCUSSION full_text_unavailable: true supporting_text_fulltext: >- These structures and organization tactics in phage infection, while not considered true VFs, are a tribute to the importance of compartmentalization in viral infection. proposed_terms: - proposed_name: phage nucleus proposed_definition: >- An intracellular membraneless organelle assembled by a bacteriophage in the cytoplasm of its bacterial host, bounded by a proteinaceous shell that encloses the replicating phage genome and separates phage DNA replication and transcription from host translation machinery and from host nucleic-acid-targeting defence systems. justification: >- The compartment term, placed by analogy with the compartments GO already models this way: GO:0031469 bacterial microcompartment and GO:0140737 encapsulin nanocompartment are both proteinaceous bacterial compartments is_a GO:0043232 intracellular membraneless organelle. That parent avoids the eukaryote-facing GO:0039713 viral factory branch, whose generalisation to prokaryotic hosts is a separate and larger question; a relationship to GO:0039713 remains desirable, since the convergence is what makes the structure interesting. proposed_parent: id: GO:0043232 label: intracellular membraneless organelle supported_by: - reference_id: PMID:28082593 reference_section_type: ABSTRACT supporting_text: >- Using fluorescence microscopy and cryo-electron tomography, we showed that Pseudomonas chlororaphis phage 201φ2-1 assembled a compartment that separated viral DNA from the cytoplasm. - proposed_name: structural constituent of phage nuclear shell proposed_definition: >- The action of a molecule that contributes to the structural integrity of the proteinaceous shell bounding a phage nucleus, a single-layer lattice perforated by pores of about 2 nm that admits nucleotides and small proteins while excluding host ribosomes and host nucleic-acid-targeting nucleases. justification: >- A molecular function rather than a second component term, following GO's existing treatment of proteinaceous shells: the carboxysome shell has no component term of its own, and shell subunits are annotated to GO:0043886 structural constituent of carboxysome shell. This is what chimallin actually needs - it is currently reduced to GO:0005198 structural molecule activity, the most generic term in the branch, which says nothing about what it builds. Proposing it as a function also sidesteps the is_a/part_of trap: a shell is not a kind of compartment, and GO's answer here is not to make it a component at all. proposed_parent: id: GO:0005198 label: structural molecule activity supported_by: - reference_id: PMID:35922510 reference_section_type: ABSTRACT supporting_text: >- In response, one family of large bacteriophages uses a nucleus-like compartment to protect its replicating genomes by excluding host defence factors - reference_id: PMID:28082593 reference_section_type: ABSTRACT supporting_text: >- Using fluorescence microscopy and cryo-electron tomography, we showed that Pseudomonas chlororaphis phage 201φ2-1 assembled a compartment that separated viral DNA from the cytoplasm. - gap_statement: >- GO's viral-factory compartment terms are essentially uncurated for the phase-separated factories, even where the scaffold protein and the LLPS mechanism are established. boundary: >- GO:0039713 viral factory and its cytoplasmic, nuclear and double-membrane vesicle children do carry reviewed UniProt annotations (reovirus mu-NS, HSV-1 ICP8, coronavirus pp1a), but GO:0039716 viroplasm viral factory and GO:0039717 spherule viral factory have none, and none of the best-characterised condensate scaffolds - rabies N/P, measles N/P, Ebola NP, rotavirus NSP2/NSP5, vaccinia H5 - carries any viral-factory term, although SARS-CoV-2 N does carry GO:0140693 molecular condensate scaffold activity. gap_kind: - CURATION dark_aspect: CC_DARK status: OPEN significance: >- The LLPS factories are where the mechanism is best understood and the annotation is thinnest, so any GO-based survey of viral factories will systematically under-represent exactly the lineages the field has moved to. resolution: >- Curate GO:0039716 / GO:0039714 onto the nucleoprotein/phosphoprotein pairs and viroplasm proteins cited in this module, GO:0039717 onto the spherule exemplars (the chikungunya and tombusvirus annotons here are concrete candidates, and GO:0039717 currently has no reviewed annotation at all), and GO:0140693 wherever the scaffolding role is demonstrated. provenance: - reference_id: PMID:34524703 reference_section_type: ABSTRACT supporting_text: >- Here we show that replication factories of rotaviruses represent protein-RNA condensates that are formed via liquid-liquid phase separation of the viroplasm-forming proteins NSP5 and rotavirus RNA chaperone NSP2. - gap_statement: >- The viral factor(s) that recruit host mitochondria to the factory periphery, and the mechanism by which the Marseilleviridae virion transiently recruits host nuclear transcription machinery to a cytoplasmic factory, are both unidentified. boundary: >- Both recruitments are established phenomenologically. Mitochondrial clustering around the ASFV factory is a directed, microtubule-dependent migration, blocked by nocodazole; and Marseilleviridae virions are known not to carry their own transcription machinery, making the recruitment necessary rather than incidental. What is missing in each case is the identity of the protein that does the recruiting. gap_kind: - BIOLOGY dark_aspect: MF_DARK status: OPEN significance: >- These are the two host-recruitment steps the module cannot ground to any participant, so the host-recruitment part stays abstract exactly where the viral effector would be the drug target. resolution: >- Identify the viral gene products required for mitochondrial repositioning and for nuclear-factor recruitment (e.g. by targeted deletion combined with the imaging assays already established in these systems). provenance: - reference_id: PMID:9696857 reference_section_type: ABSTRACT supporting_text: >- The clustering of mitochondria around the viral factory was blocked in the presence of the microtubule-disassembling drug nocodazole, indicating that these filaments are implicated in the transport of the mitochondria to the virus assembly sites. - reference_id: PMID:28429720 reference_section_type: ABSTRACT supporting_text: >- Unexpectedly, we find that their virions do not incorporate the virus-encoded transcription machinery, making their replication nucleus-dependent. - gap_statement: >- GO has no term for evading a host CRISPR-Cas system, only one for suppressing it, so the best-characterised case of compartmentalisation defeating host immunity cannot be annotated with the mechanism it demonstrates. boundary: >- The mechanism is settled, not uncertain. The phage shell does not inhibit or disrupt CRISPR-Cas: the system remains functional and is defeated spatially, which is exactly what the two controls show - relocalising EcoRI inside the compartment restores targeting, and RNA-targeting Cas13a remains effective because phage mRNA leaves the shell. GO already draws this distinction elsewhere in the same area: GO:0099018 symbiont-mediated evasion of host restriction-modification system sits under GO:0141177 (evasion of recognition by a host innate immune effector), while GO:0098672 symbiont-mediated suppression of host CRISPR-cas system sits under GO:0052031 (perturbation of host defense response). Only the suppression branch has a CRISPR member. gap_kind: - ONTOLOGY dark_aspect: BP_DARK status: OPEN significance: >- Annotating chimallin to GO:0098672 asserts that the shell perturbs the host's CRISPR-Cas system, which is the opposite of the paper's finding. Any analysis grouping anti-CRISPR mechanisms would place a steric barrier alongside Acr proteins that bind and inhibit Cas complexes. This module nevertheless keeps GO:0098672 on vf_chimallin_nuclease_exclusion, and the trade is deliberate: the schema has no way for an annoton to point at a proposed term, so dropping the only CRISPR-facing term would leave the CRISPR half of the shell's demonstrated activity with no assertion at all. The annoton carries the term together with a description saying it misdescribes the mechanism, on the view that a flagged over-broad assertion is more useful to a reader than silence. Replace it if the proposed term is created. resolution: >- A term such as "symbiont-mediated evasion of host CRISPR-cas system" under GO:0141177, sibling to GO:0099018, letting the two halves of the shell's exclusion activity be annotated on the same branch. provenance: - reference_id: PMID:31819262 reference_section_type: ABSTRACT supporting_text: >- Cas proteins and restriction enzymes are unable to access the phage DNA throughout the infection, but engineering the relocalization of EcoRI inside the compartment enables targeting of the phage and protection of host cells. proposed_terms: - proposed_name: symbiont-mediated evasion of host CRISPR-cas system proposed_definition: >- A process by which a symbiont avoids the effect of its host's CRISPR-Cas system without inhibiting or disrupting that system, for example by sequestering its genome in a compartment the Cas effector cannot enter. justification: >- GO:0098672 is the only CRISPR-facing term and it is a suppression term; the compartmentalisation mechanism is evasion. The parallel term for the restriction-modification arm, GO:0099018, already exists on the evasion branch, so the asymmetry looks like an omission rather than a deliberate modelling choice. proposed_parent: id: GO:0141177 label: symbiont-mediated evasion of recognition by host innate immune effector supported_by: - reference_id: PMID:31819262 reference_section_type: ABSTRACT supporting_text: >- Here we show that jumbo phage ΦKZ segregates its DNA from immunity nucleases of its host, Pseudomonas aeruginosa, by constructing a proteinaceous nucleus-like compartment. module: id: viral_factory label: Viral factory (virus-induced replication microcompartment) module_type: ORGANELLE_LIFECYCLE description: >- Biogenesis and operation of the virus-induced compartment: a boundary is drawn in the host cell, host systems are recruited to and around it, viral transcription and genome replication run inside it, progeny virions are assembled and packaged within it, and replication intermediates are screened from host defences throughout. concepts: - preferred_term: viral factory term: id: GO:0039713 label: viral factory description: >- The compartment itself. GO's definition already couples the two functions this module separates into parts: raising replication efficiency, and shielding the virus from host defences. - preferred_term: viral replication complex formation and maintenance term: id: GO:0046786 label: viral replication complex formation and maintenance description: The process view of factory biogenesis. - preferred_term: viral replication complex term: id: GO:0019034 label: viral replication complex context: taxa: - preferred_term: Viruses term: id: NCBITaxon:10239 label: Viruses description: >- The module spans RNA and DNA viruses of eukaryotes; the protein-shell boundary variant extends it to jumbo phages of bacteria. cellular_components: - preferred_term: host cell cytoplasm term: id: GO:0030430 label: host cell cytoplasm description: >- The default location; nuclear factories (herpesviruses, adenoviruses, polyomaviruses, EBV) are the alternative and are modelled on the condensate and membrane variants where relevant. conditions: - preferred_term: productive infection of a host cell description: >- The factory exists only during infection; it is built, used, and dispersed within one replication cycle rather than inherited. - preferred_term: compartment boundary mechanism is lineage-specific description: >- Membrane-derived, condensate, and proteinaceous-shell boundaries are alternative solutions to the same problem, and a single virus may use more than one (SARS-CoV-2 uses double-membrane vesicles for RNA synthesis and a separate nucleoprotein condensate for packaging). parts: - order: 1 role: compartment boundary formation node: id: vf_boundary label: Compartment nucleation and boundary formation module_type: CELLULAR_COMPONENT description: >- Establishment of the physical boundary that separates factory contents from bulk cytoplasm or nucleoplasm. The boundary is what makes the factory a compartment; the variants below are the three physically distinct ways it is drawn. concepts: - preferred_term: viral factory term: id: GO:0039713 label: viral factory variant_sets: - id: vf_boundary_mechanism_axis label: Compartment boundary mechanism axis: physical basis of the compartment boundary selection: ONE_OR_MORE notes: >- ONE_OR_MORE rather than EXACTLY_ONE: coronaviruses run a membrane-bounded replication organelle and a separate nucleoprotein condensate in the same cell, and Chimalliviridae pass through a membrane-bound vesicle before building the protein shell. variants: - id: vf_membrane_boundary label: Host-membrane-derived boundary module_type: CELLULAR_COMPONENT description: >- The boundary is a host membrane deformed by viral proteins into an invagination (spherule), a tube, a double-membrane vesicle, or a convoluted network. The lumen is topologically separated from the cytosol, so a pore or neck is required to import nucleotides and export progeny RNA. concepts: - preferred_term: spherule viral factory term: id: GO:0039717 label: spherule viral factory - preferred_term: double membrane vesicle viral factory term: id: GO:0039718 label: double membrane vesicle viral factory - preferred_term: tube viral factory term: id: GO:0039719 label: tube viral factory annotons: - id: vf_membrane_remodeling label: Viral membrane-remodelling protein deforming a host organelle membrane participant: selector_type: ANY_WITH_FUNCTION required_function: preferred_term: membrane bending activity term: id: GO:0180020 label: membrane bending activity description: >- Typically a multi-spanning or amphipathic-helix-bearing non-structural protein of the replicase (coronavirus nsp3/nsp4/nsp6, flavivirus NS4A/NS4B, alphavirus nsP1, tombusvirus p33). function: preferred_term: membrane bending activity term: id: GO:0180020 label: membrane bending activity targets: - preferred_term: host endomembrane donating the factory boundary processes: - preferred_term: symbiont-mediated perturbation of host membrane term: id: GO:0141171 label: symbiont-mediated perturbation of host membrane role_description: >- Deforms a donor host membrane into the closed or necked geometry that defines the factory lumen. evidence: - source_id: PMID:19380115 title: Composition and three-dimensional architecture of the dengue virus replication and assembly sites. statement: >- Establishes an ER-derived, vesicle-and-pore boundary containing the dsRNA replication intermediate. supporting_text: >- Using electron microscopy, we find Dengue virus (DENV)-induced vesicles, convoluted membranes, and virus particles to be endoplasmic reticulum (ER)-derived, and we detect double-stranded RNA, a presumed marker of RNA replication, inside virus-induced vesicles. - id: vf_dmv_export_pore label: Double-membrane-spanning export pore of the coronavirus replication organelle participant: selector_type: GENE_PRODUCT gene_product: preferred_term: SARS-CoV-2 replicase polyprotein 1a (nsp3 pore component) term: id: UniProtKB:P0DTC1 label: Replicase polyprotein 1a description: >- Carries GO:0039718 double membrane vesicle viral factory in UniProt. The pore core is a hexameric assembly of a large viral transmembrane protein released from this polyprotein; the original study identifies nsp3 as the leading candidate subunit rather than establishing it. locations: - preferred_term: double membrane vesicle viral factory term: id: GO:0039718 label: double membrane vesicle viral factory - preferred_term: double membrane vesicle viral factory membrane term: id: GO:0062242 label: double membrane vesicle viral factory membrane processes: - preferred_term: double membrane vesicle viral factory assembly term: id: GO:0140526 label: double membrane vesicle viral factory assembly role_description: >- Solves the topological problem created by a sealed membrane boundary: exports newly synthesised genomes and mRNAs from the DMV lumen to the cytosol for translation and packaging. No molecular-function term is asserted - the pore's transport activity has not been reconstituted. evidence: - source_id: PMID:32763915 title: A molecular pore spans the double membrane of the coronavirus replication organelle. statement: Establishes the pore and its role in RNA export from the sealed DMV. supporting_text: >- In this study, we used cellular cryo-electron microscopy to visualize a molecular pore complex that spans both membranes of the double-membrane vesicle and would allow export of RNA to the cytosol. - source_id: PMID:32511245 title: "A unifying structural and functional model of the coronavirus replication organelle: Tracking down RNA synthesis." statement: >- Establishes the DMV, rather than any other virus-induced membrane structure, as the site of coronaviral RNA synthesis. supporting_text: >- Our results provide a unifying model of the CoV RO and clearly establish DMVs as the central hub for viral RNA synthesis and a potential drug target in CoV infection. variant_sets: - id: vf_membrane_donor_axis label: Host organelle donating the boundary membrane axis: donor organelle selection: EXACTLY_ONE notes: >- The donor is a fixed, lineage-specific choice, which is why this axis is EXACTLY_ONE while the boundary-mechanism axis above is not. variants: - id: vf_er_ergic_donor label: Endoplasmic reticulum / ERGIC-derived boundary module_type: CELLULAR_COMPONENT description: >- Flaviviruses invaginate the rough ER into vesicle packets and convoluted membranes; coronaviruses derive double-membrane vesicles from the ER-Golgi intermediate compartment. context: cellular_components: - preferred_term: host cell endoplasmic reticulum term: id: GO:0044165 label: host cell endoplasmic reticulum - preferred_term: host cell endoplasmic reticulum-Golgi intermediate compartment term: id: GO:0044172 label: host cell endoplasmic reticulum-Golgi intermediate compartment annotons: - id: vf_dengue_er_invagination label: Flaviviral polyprotein driving ER invagination participant: selector_type: GENE_PRODUCT gene_product: preferred_term: Dengue virus 2 genome polyprotein (NS4A/NS4B membrane-remodelling region) term: id: UniProtKB:P18356 label: Genome polyprotein locations: - preferred_term: host cell endoplasmic reticulum term: id: GO:0044165 label: host cell endoplasmic reticulum processes: - preferred_term: viral RNA genome replication term: id: GO:0039694 label: viral RNA genome replication role_description: >- Representative of the flaviviral replication organelle: a single ER-derived network carrying both the replication vesicles and, apposed to their pores, the budding sites. evidence: - source_id: PMID:19380115 statement: >- Establishes that the vesicles, convoluted membranes, and budding particles form one ER-derived network. supporting_text: >- Electron tomography (ET) shows DENV-induced membrane structures to be part of one ER-derived network. - id: vf_plasma_membrane_donor label: Plasma-membrane-derived boundary module_type: CELLULAR_COMPONENT description: >- Alphaviruses generate spherules by deforming the host plasma membrane; in chikungunya virus these persist at the plasma membrane rather than being internalised. context: cellular_components: - preferred_term: host cell plasma membrane term: id: GO:0020002 label: host cell plasma membrane annotons: - id: vf_alphavirus_spherule label: Alphaviral non-structural polyprotein forming a plasma-membrane spherule participant: selector_type: GENE_PRODUCT gene_product: preferred_term: Chikungunya virus non-structural polyprotein P1234 term: id: UniProtKB:Q8JUX6 label: Polyprotein P1234 description: >- Carries GO:0020002 host cell plasma membrane in UniProt; nsP1 provides the membrane-binding amphipathic anchor and nsP4 the polymerase. function: preferred_term: RNA-directed RNA polymerase activity term: id: GO:0003968 label: RNA-directed RNA polymerase activity locations: - preferred_term: host cell plasma membrane term: id: GO:0020002 label: host cell plasma membrane processes: - preferred_term: viral RNA genome replication term: id: GO:0039694 label: viral RNA genome replication role_description: >- Occupies the spherule and synthesises RNA inside it; the replication complex sits at the spherule neck, which stays open to the cytosol so nascent RNA is extruded rather than exported through a pore. The boundary-shaping half of this variant's claim is asserted separately on the nsP1 annoton below, which is the cleavage product that carries it. evidence: - source_id: PMID:38940586 title: In situ fate of Chikungunya virus replication organelles. statement: >- Establishes the spherule as the membranous replication organelle housing the replication complex. supporting_text: >- Replication of the viral RNA genome occurs in specialized membranous replication organelles (ROs) or spherules, which contain the viral replication complex. - source_id: PMID:38940586 statement: >- Supports persistence and continued growth of the plasma-membrane spherule rather than its internalisation. supporting_text: >- We evidence the late persistence of CHIKV ROs at the plasma membrane with a crowned protein complex at the spherule neck similar to the recently resolved replication complex. - id: vf_alphavirus_nsp1_membrane_shaping label: Alphaviral nsP1 ring shaping and sealing the spherule neck participant: selector_type: GENE_PRODUCT gene_product: preferred_term: Chikungunya virus mRNA-capping enzyme nsP1 term: id: UniProtKB:Q8JUX6 label: Polyprotein P1234 description: >- The same polyprotein as the annoton above, named here for its nsP1 cleavage product. Two annotons rather than one because the membrane-shaping and polymerase activities are carried by different mature products and the boundary is what this part of the module is about. function: preferred_term: membrane bending activity term: id: GO:0180020 label: membrane bending activity description: >- Asserted on the amphipathic-insertion mechanism GO:0180020's definition names explicitly. This is a module-level assertion, not a curated UniProt annotation. locations: - preferred_term: host cell plasma membrane term: id: GO:0020002 label: host cell plasma membrane processes: - preferred_term: symbiont-mediated perturbation of host membrane term: id: GO:0141171 label: symbiont-mediated perturbation of host membrane role_description: >- Grounds the boundary-forming activity this part models in a concrete exemplar: a dodecameric ring that inserts amphipathic spikes into the host plasma membrane, anchors the replication complex to it, and forms the pore at the spherule neck. evidence: - source_id: PMID:38940586 statement: >- Establishes the membrane-deforming mechanism as amphipathic insertion, which is one of the mechanisms GO:0180020 is defined over. supporting_text: >- which forms amphipathic membrane-binding spikes penetrating by about 10 Å into detergent FC12 micelles - source_id: PMID:38940586 statement: >- Establishes that nsP1 both anchors the replication complex to the bilayer and constitutes the neck structure separating spherule lumen from cytoplasm. supporting_text: >- supported the assembly of an nsP1 connecting pore separating the inner part of the spherule from the cytoplasm - id: vf_peroxisome_donor label: Peroxisome-derived boundary module_type: CELLULAR_COMPONENT description: >- Tombusviruses build spherules on the peroxisomal boundary membrane (and on the ER when peroxisomes are absent), the clearest case of a factory boundary drawn on an organelle unrelated to the secretory pathway. context: cellular_components: - preferred_term: host cell peroxisome term: id: GO:0120149 label: host cell peroxisome annotons: - id: vf_tombusvirus_spherule label: Tombusviral replication protein forming a peroxisomal spherule participant: selector_type: GENE_PRODUCT gene_product: preferred_term: Tomato bushy stunt virus p92 replicase (and its p33 cleavage product) term: id: UniProtKB:P15962 label: RNA-directed RNA polymerase description: >- p33, the N-terminal product of this ORF, is the membrane-bound spherule-forming protein; p92 is the read-through polymerase. function: preferred_term: RNA-directed RNA polymerase activity term: id: GO:0003968 label: RNA-directed RNA polymerase activity processes: - preferred_term: viral RNA genome replication term: id: GO:0039694 label: viral RNA genome replication role_description: >- Replicase that carries out RNA synthesis inside the spherule. The spherule-nucleating role is attributed to its p33 cleavage product rather than to the polymerase, and no membrane-shaping function is asserted here: unlike the alphavirus case above, no reference in this module establishes the mechanism, so this donor variant grounds the location and the polymerase only. evidence: - source_id: PMID:42734359 statement: >- Source review: places tombusvirus and bromovirus spherules on host peroxisomes and ER respectively. notes: >- Claim taken from the review body. Only the abstract of this review is cached locally, so no verbatim quote is asserted here. - id: vf_condensate_boundary label: Biomolecular condensate boundary (liquid-liquid phase separation) module_type: CELLULAR_COMPONENT description: >- The boundary is a phase boundary rather than a membrane: viral scaffold proteins with intrinsically disordered regions, in concert with the viral genome, demix from the cytoplasm or nucleoplasm into a liquid condensate. Because the boundary is permeable to small molecules and to diffusing macromolecules, no pore is needed; concentration and selective partitioning do the work instead. The recurring architecture across Mononegavirales is a nucleoprotein-phosphoprotein pair, at least one of which contributes an essential disordered region. concepts: - preferred_term: viroplasm viral factory term: id: GO:0039716 label: viroplasm viral factory - preferred_term: cytoplasmic viral factory term: id: GO:0039714 label: cytoplasmic viral factory - preferred_term: nuclear viral factory term: id: GO:0039715 label: nuclear viral factory description: >- The nuclear case: EBV EBNA2/EBNALP condensates form in the nucleus rather than the cytoplasm. annotons: - id: vf_nucleoprotein_condensate_scaffold label: Mononegavirales nucleoprotein condensate scaffold participant: selector_type: FAMILY family: preferred_term: Mononegavirales nucleoprotein (N/NP) description: >- No PANTHER family is asserted: these are viral nucleoproteins outside PANTHER's classification, so the descriptor is grounded by representative members only. Representatives are reference entries from different strains of each virus. representative_members: - preferred_term: N (rabies virus nucleoprotein) term: id: UniProtKB:P16285 label: Nucleoprotein - preferred_term: N (measles virus nucleoprotein) term: id: UniProtKB:P04851 label: Nucleoprotein - preferred_term: NP (Zaire ebolavirus nucleoprotein) term: id: UniProtKB:P18272 label: Nucleoprotein function: preferred_term: molecular condensate scaffold activity term: id: GO:0140693 label: molecular condensate scaffold activity processes: - preferred_term: viral replication complex formation and maintenance term: id: GO:0046786 label: viral replication complex formation and maintenance locations: - preferred_term: cytoplasmic viral factory term: id: GO:0039714 label: cytoplasmic viral factory role_description: >- Principal mass of the condensate and the RNA-binding partner; encapsidates nascent genomes into nucleocapsids within the droplet, where the encapsidation rate is higher than in the dilute phase. evidence: - source_id: PMID:28680096 title: Negri bodies are viral factories with properties of liquid organelles. statement: >- Establishes the rabies virus factory as a liquid organelle and the N+P pair as sufficient to build it. supporting_text: >- Coexpression of rabies virus N and P proteins results in cytoplasmic inclusions recapitulating NBs properties. - source_id: PMID:32270045 title: Measles virus nucleo- and phosphoproteins form liquid-like phase-separated compartments that promote nucleocapsid assembly. statement: >- Establishes that the condensate accelerates the reaction it houses - a functional, not merely architectural, role for the boundary. supporting_text: >- The rate of encapsidation within droplets is enhanced compared to the dilute phase, revealing one of the roles of liquid-liquid phase separation in measles virus replication. - source_id: PMID:37443171 title: Spatial and functional arrangement of Ebola virus polymerase inside phase-separated viral factories. statement: >- Extends the condensate architecture to filoviruses and shows internal spatial organisation within the droplet. supporting_text: >- We show that intracellularly reconstituted EBOV viral factories are biomolecular condensates, with composition-dependent internal exchange dynamics that likely facilitates viral replication. - id: vf_phosphoprotein_condensate_partner label: Mononegavirales phosphoprotein condensate partner participant: selector_type: FAMILY family: preferred_term: Mononegavirales phosphoprotein (P) description: >- Grounded by representative members only; no PANTHER family covers these proteins. representative_members: - preferred_term: P (rabies virus phosphoprotein) term: id: UniProtKB:P69479 label: Phosphoprotein - preferred_term: P (measles virus phosphoprotein) term: id: UniProtKB:P03422 label: Phosphoprotein function: preferred_term: molecular condensate scaffold activity term: id: GO:0140693 label: molecular condensate scaffold activity processes: - preferred_term: viral transcription term: id: GO:0019083 label: viral transcription role_description: >- Supplies the intrinsically disordered region and the dimerization domain required for demixing, and tethers the L polymerase to the N-RNA template inside the condensate. In rabies virus both elements of P are individually essential for Negri-body-like structures to form. evidence: - source_id: PMID:28680096 statement: >- Identifies the specific P determinants required for condensate formation. supporting_text: >- This minimal system reveals that an intrinsically disordered domain and the dimerization domain of P are essential for Negri bodies-like structures formation. - id: vf_coronavirus_n_condensate label: Coronaviral nucleocapsid protein condensate for genome packaging participant: selector_type: GENE_PRODUCT gene_product: preferred_term: SARS-CoV-2 nucleoprotein N term: id: UniProtKB:P0DTC9 label: Nucleoprotein description: >- Already carries GO:0140693 molecular condensate scaffold activity and GO:0019074 viral RNA genome packaging in UniProt. function: preferred_term: molecular condensate scaffold activity term: id: GO:0140693 label: molecular condensate scaffold activity processes: - preferred_term: viral RNA genome packaging term: id: GO:0019074 label: viral RNA genome packaging locations: - preferred_term: host cell cytoplasm term: id: GO:0030430 label: host cell cytoplasm role_description: >- The second, condensate-based factory site of a virus whose RNA synthesis happens in a membrane-bounded organelle: packaging is spatially separated from replication, which is why the boundary-mechanism axis is ONE_OR_MORE. evidence: - source_id: PMID:42734359 statement: >- Source review: places the SARS-CoV-2 N condensate as a distinct second factory site alongside the DMVs. notes: >- Claim taken from the review body; only the abstract is cached locally, so no verbatim quote is asserted. The independent grounding for this annoton is the curated GO:0140693 annotation on UniProtKB:P0DTC9. - id: vf_rotavirus_viroplasm_condensate label: Rotavirus NSP2-NSP5 viroplasm condensate participant: selector_type: PROTEIN_COMPLEX protein_complex: preferred_term: Rotavirus viroplasm-forming NSP2-NSP5 condensate description: >- Modelled as a two-unit assembly rather than a named GO complex: no protein-complex term exists for it, and the partners are the minimal sufficient pair for condensate formation in vitro. active_units: - id: vf_rota_nsp5_unit label: NSP5 (viroplasm-forming phosphoprotein) participant: selector_type: GENE_PRODUCT gene_product: preferred_term: Rotavirus A SA11 non-structural protein 5 term: id: UniProtKB:A2T3Q9 label: Non-structural protein 5 role: >- Condensate-forming partner whose hyperphosphorylation during late infection hardens the condensate's material properties. - id: vf_rota_nsp2_unit label: NSP2 (RNA chaperone) participant: selector_type: GENE_PRODUCT gene_product: preferred_term: Rotavirus A SA11 non-structural protein 2 term: id: UniProtKB:A2T3P0 label: Non-structural protein 2 role: RNA chaperone partner; brings viral transcripts into the condensate. processes: - preferred_term: viral genome replication term: id: GO:0019079 label: viral genome replication locations: - preferred_term: viroplasm viral factory term: id: GO:0039716 label: viroplasm viral factory role_description: >- Protein-RNA condensate in which the eleven genome segments of a segmented dsRNA virus are co-packaged; the one case where the factory's material properties are shown to change over the infection cycle. evidence: - source_id: PMID:34524703 title: Liquid-liquid phase separation underpins the formation of replication factories in rotaviruses. statement: Establishes the NSP5/NSP2 condensate as the rotavirus replication factory. supporting_text: >- Here we show that replication factories of rotaviruses represent protein-RNA condensates that are formed via liquid-liquid phase separation of the viroplasm-forming proteins NSP5 and rotavirus RNA chaperone NSP2. - source_id: PMID:34524703 statement: >- Establishes that the condensate's material state is regulated across the infection cycle. supporting_text: >- During late infection, these condensates exhibited altered material properties and became resistant to propylene glycol, coinciding with hyperphosphorylation of NSP5. - id: vf_poxvirus_h5_condensate label: Poxviral H5 condensate nucleating the cytoplasmic factory participant: selector_type: GENE_PRODUCT gene_product: preferred_term: Vaccinia virus H5 (OPG110) term: id: UniProtKB:P07242 label: Late transcription elongation factor OPG110 description: >- Carries GO:0039693 viral DNA genome replication and GO:0019083 viral transcription in UniProt; the condensate-scaffold role is the addition proposed here. function: preferred_term: molecular condensate scaffold activity term: id: GO:0140693 label: molecular condensate scaffold activity processes: - preferred_term: viral DNA genome replication term: id: GO:0039693 label: viral DNA genome replication locations: - preferred_term: host cell cytoplasm term: id: GO:0030430 label: host cell cytoplasm role_description: >- Demonstrates that condensate boundaries are not restricted to RNA viruses: a DNA-binding poxviral protein phase separates through its N-terminal IDR, and DNA binding is required for both the phase separation and factory assembly. The same behaviour is seen for H5 orthologs of mpox virus and lumpy skin disease virus. evidence: - source_id: PMID:41264624 title: Poxvirus H5 mediates the formation of liquid-liquid phase separation condensates which promote virus factory assembly. statement: Establishes H5-driven LLPS. supporting_text: >- Here, we report that H5, a DNA-binding protein of vaccinia virus (VACV) could undergo LLPS through its N-terminal intrinsically disordered region (IDR). - source_id: PMID:41264624 statement: >- Establishes that the condensate is required for factory assembly and productive replication, not merely correlated with it. supporting_text: >- Mutations at these residues inhibit the binding of H5 to DNA, thereby directly or indirectly abolish LLPS formation, and impair viral replication factory assembly, leading to a marked reduction in viral DNA replication and progeny production - id: vf_nuclear_condensate_ebna2 label: Nuclear condensate factory of Epstein-Barr virus participant: selector_type: GENE_PRODUCT gene_product: preferred_term: Epstein-Barr virus nuclear antigen 2 (EBNA2) term: id: UniProtKB:P12978 label: Epstein-Barr nuclear antigen 2 function: preferred_term: molecular condensate scaffold activity term: id: GO:0140693 label: molecular condensate scaffold activity locations: - preferred_term: nuclear viral factory term: id: GO:0039715 label: nuclear viral factory role_description: >- With its coactivator EBNALP, forms nuclear liquid-like puncta enriched at host superenhancers. Included as the nuclear counterpart of the cytoplasmic condensate variant; here the condensate organises viral control of host gene expression rather than genome replication, which is the main respect in which nuclear condensate factories differ. evidence: - source_id: PMID:31941785 title: Phase Separation of Epstein-Barr Virus EBNA2 and Its Coactivator EBNALP Controls Gene Expression. statement: Establishes nuclear viral LLPS and its IDR dependence. supporting_text: >- Here, we discovered that Epstein-Barr virus (EBV) EBNA2 and EBNALP form nuclear puncta that exhibit properties of liquid-like condensates (or droplets), which are enriched in superenhancers of MYC and Runx3. - id: vf_protein_shell_boundary label: Self-assembled proteinaceous shell boundary (phage nucleus) module_type: CELLULAR_COMPONENT description: >- The boundary is a single-layer protein lattice with ~2 nm pores, built de novo by the virus rather than borrowed from the host. It is selectively permeable: nucleotides and small proteins enter, but ribosomes and host nucleases are excluded, so transcription inside is physically separated from translation outside. In Chimalliviridae this shell is preceded by a transient membrane-bound compartment, making the two boundary mechanisms sequential within one infection. notes: >- Caveat carried from the source review: these phage compartments are conventionally described as analogous to, rather than instances of, viral factories, and GO has no term for them. They are retained here as a boundary variant because they meet this module's functional definition; see the module-level ontology knowledge gap. annotons: - id: vf_chimallin_shell label: Chimallin nuclear shell lattice participant: selector_type: FAMILY family: preferred_term: Chimallin (ChmA) phage nuclear shell protein description: >- Grounded by representative members; PANTHER does not classify these phage proteins. representative_members: - preferred_term: ChmA (Pseudomonas phage 201phi2-1 chimallin gp105) term: id: UniProtKB:B3FIW8 label: Chimallin - preferred_term: ChmA (Pseudomonas phage phiKZ chimallin gp54) term: id: UniProtKB:Q8SDA8 label: Chimallin function: preferred_term: structural molecule activity term: id: GO:0005198 label: structural molecule activity description: >- The only available molecular-function grounding; no term expresses "self-assembling compartment shell subunit". locations: - preferred_term: host cell cytoplasm term: id: GO:0030430 label: host cell cytoplasm description: >- The only cellular-component term these proteins can currently carry, which is the ontology gap recorded at module level. role_description: >- Self-assembles as a flexible sheet into a closed micrometre-scale compartment around the replicating phage genome; the sole principal component of the shell. evidence: - source_id: PMID:35922510 title: Architecture and self-assembly of the jumbo bacteriophage nuclear shell. statement: Establishes chimallin as the principal and sufficient shell component. supporting_text: >- we show that chimallin self-assembles as a flexible sheet into closed micrometre-scale compartments. - source_id: PMID:28082593 title: Assembly of a nucleus-like structure during viral replication in bacteria. statement: >- Establishes functional segregation across the shell: replication and transcription inside, translation outside. supporting_text: >- Proteins involved in DNA replication and transcription localized inside the compartment, whereas proteins involved in translation and nucleotide synthesis localized outside. - source_id: PMID:37667030 title: Identification of the bacteriophage nucleus protein interaction network. statement: >- Supports treating the shell as an interaction hub with accessory components rather than a bare lattice, and identifies the component that makes it a docking surface for packaging. supporting_text: >- The structure and protein-protein interaction network of this protein, which we term ChmB, suggest that it forms pores in the ChmA lattice that serve as docking sites for capsid genome packaging and may also participate in messenger RNA and/or protein translocation. - id: vf_epi_vesicle_precursor label: Membrane-bound early phage infection vesicle preceding the shell participant: selector_type: ANY_PARTICIPANT description: >- The protein(s) that build or maintain the EPI vesicle membrane compartment are not identified; the compartment is defined by imaging and by the arrest phenotype. processes: - preferred_term: DNA-templated viral transcription term: id: GO:0039695 label: DNA-templated viral transcription locations: - preferred_term: host cell cytoplasm term: id: GO:0030430 label: host cell cytoplasm role_description: >- A transcriptionally active, membrane-bound compartment that holds the injected genome before it is transferred into the chimallin shell; genome replication begins only after that transfer. Establishes that the two boundary mechanisms are used in sequence, not as alternatives, in this lineage. evidence: - source_id: PMID:40168997 title: Sequential membrane- and protein-bound organelles compartmentalize genomes during phage infection. statement: Establishes the EPI vesicle as a functional precursor compartment. supporting_text: >- Early phage genes are expressed from the EPI vesicle, demonstrating its functionality as a prokaryotic, transcriptionally active, membrane-bound organelle. - source_id: PMID:40168997 statement: >- Establishes the ordering: transfer into the phage nucleus is a precondition for genome replication. supporting_text: >- We also show that the phage nucleus is essential, with genome replication beginning after the injected DNA is transferred from the EPI vesicle to the phage nucleus. - order: 2 role: host system recruitment node: id: vf_host_recruitment label: Recruitment and remodelling of host systems around the factory module_type: BIOLOGICAL_PROCESS description: >- The factory is not self-sufficient. It draws in host membranes and lipids for its boundary, host cytoskeleton for its position and structural integrity, host mitochondria for the ATP its morphogenesis consumes, and in some lineages host transcription factors it does not encode. These recruitments are modelled as a variant set because different viruses recruit different subsets, not as a fixed sequence. evidence: - source_id: PMID:42734359 statement: Source review framing for this part. supporting_text: >- VFs recruit host lipids, cytoskeletal elements, and metabolic enzymes, effectively reprogramming the intracellular environment to favor viral replication. variant_sets: - id: vf_recruited_host_system_axis label: Recruited host system axis: host system co-opted by the factory selection: ONE_OR_MORE variants: - id: vf_intermediate_filament_cage label: Intermediate filament cage around the factory module_type: MODULE description: >- Vimentin collapses from its dispersed cytoplasmic network into a cage surrounding the perinuclear factory, the same rearrangement the cell makes around an aggresome. This is the strongest evidence that factories of the large cytoplasmic DNA viruses co-opt a pre-existing host response rather than building a structure from scratch. annotons: - id: vf_vimentin_cage label: Host vimentin forming the factory cage participant: selector_type: GENE_PRODUCT gene_product: preferred_term: human vimentin term: id: UniProtKB:P08670 label: Vimentin description: >- Host, not viral: this annoton records a host protein recruited by the factory. function: preferred_term: structural constituent of cytoskeleton term: id: GO:0005200 label: structural constituent of cytoskeleton locations: - preferred_term: intermediate filament term: id: GO:0005882 label: intermediate filament role_description: >- Structural cage enclosing the factory. PMID:11331297 shows that ASFV factories and aggresomes share the same vimentin rearrangement, that both assemble near the microtubule organizing center, and that both require an intact microtubule network - but it establishes the cage correlatively and does not test whether vimentin is required for factory integrity. The source review also reports a vimentin requirement for Ebola virus factories; that claim is not repeated here because no reference in this module supports it. evidence: - source_id: PMID:11331297 title: Aggresomes resemble sites specialized for virus assembly. statement: >- Establishes the vimentin cage and mitochondrial recruitment as shared between aggresomes and ASFV factories. supporting_text: >- Both structures caused rearrangement of intermediate filaments and the collapse of vimentin into characteristic cages, and both recruited mitochondria and cellular chaperones. - id: vf_mitochondrial_recruitment label: Mitochondrial recruitment to the factory periphery module_type: MODULE description: >- Mitochondria migrate en masse along microtubules to the factory and cluster at its periphery, adopting the ultrastructure of actively respiring organelles. The recruitment is selective for factories containing assembling particles rather than precursor membranes, consistent with supplying the ATP that morphogenesis consumes. annotons: - id: vf_mitochondrion_recruitment label: Directed migration of host mitochondria to the factory participant: selector_type: ANY_PARTICIPANT description: >- The viral factor that triggers or targets the migration is unidentified; see the module-level knowledge gap. locations: - preferred_term: host cell mitochondrion term: id: GO:0033650 label: host cell mitochondrion role_description: >- Places an ATP source immediately outside the factory boundary during the assembly phase. evidence: - source_id: PMID:9696857 title: Migration of mitochondria to viral assembly sites in African swine fever virus-infected cells. statement: Establishes active, directed recruitment rather than passive co-localisation. supporting_text: >- Immunofluorescence microscopy revealed that these accumulations of mitochondria are originated by a massive migration of the organelle to the virus assembly sites. - source_id: PMID:9696857 statement: >- Supports selectivity for assembly-stage factories, the basis for the energetic interpretation. supporting_text: >- These clusters surround viral factories that contain assembling particles but not factories where only precursor membranes are seen. - id: vf_lipid_microenvironment label: Host lipid-kinase recruitment generating a distinct membrane lipid composition module_type: MODULE description: >- Picornaviral and some flaviviral replication organelles are not merely shaped host membrane but chemically distinct from it: viral proteins redirect Arf1/GBF1 effector recruitment to enrich the organelle in phosphatidylinositol-4-phosphate, which the viral RNA polymerase binds directly. annotons: - id: vf_pi4k_recruitment label: Host phosphatidylinositol 4-kinase generating the PI4P-rich factory membrane participant: selector_type: GENE_PRODUCT gene_product: preferred_term: human phosphatidylinositol 4-kinase beta (PI4KB) term: id: UniProtKB:Q9UBF8 label: Phosphatidylinositol 4-kinase beta function: preferred_term: 1-phosphatidylinositol 4-kinase activity term: id: GO:0004430 label: 1-phosphatidylinositol 4-kinase activity role_description: >- Host enzyme recruited to the nascent replication organelle; its product PI4P both defines the organelle's lipid identity and is the direct binding partner of the viral RNA-dependent RNA polymerase, coupling membrane composition to polymerase localisation. evidence: - source_id: PMID:20510927 title: Viral reorganization of the secretory pathway generates distinct organelles for RNA replication. statement: Establishes PI4P as functionally required, not merely enriched. supporting_text: >- The PI4P-rich lipid microenvironment is essential for both enteroviral and flaviviral RNA replication; PI4KIIIbeta inhibition interferes with this process; and enteroviral RNA polymerases specifically bind PI4P. - id: vf_host_transcription_machinery_recruitment label: Transient recruitment of host nuclear transcription machinery module_type: MODULE description: >- Marseilleviridae were assumed to be fully cytoplasmic on gene content alone, but their virions do not package a transcription apparatus. Instead the factory transiently draws host nuclear transcription machinery out to the cytoplasm, the host nucleus becoming briefly leaky and then recovering. A striking case of a factory importing a function rather than encoding it. annotons: - id: vf_nuclear_factor_recruitment label: Recruitment of host nuclear transcription machinery to the cytoplasmic factory participant: selector_type: ANY_PARTICIPANT description: >- The virion-delivered factor responsible is unidentified; see the module-level knowledge gap. processes: - preferred_term: DNA-templated viral transcription term: id: GO:0039695 label: DNA-templated viral transcription locations: - preferred_term: cytoplasmic viral factory term: id: GO:0039714 label: cytoplasmic viral factory role_description: >- Supplies the transcription activity the virion does not carry, making an otherwise cytoplasmic replication cycle nucleus-dependent. evidence: - source_id: PMID:28429720 title: Noumeavirus replication relies on a transient remote control of the host nucleus. statement: Establishes the recruitment and its transience. supporting_text: >- However, instead of delivering their DNA to the nucleus, the Marseilleviridae initiate their replication by transiently recruiting the nuclear transcription machinery to their cytoplasmic viral factory. - id: vf_phage_spindle_positioning label: Phage tubulin spindle positioning the factory module_type: MODULE description: >- The bacterial counterpart of cytoskeletal recruitment, except that the cytoskeleton is virus-encoded: a tubulin-like protein builds a bipolar spindle that pushes the phage nucleus to midcell and holds it there. Capsids are trafficked to the shell surface for packaging, but no reference cited in this module attributes that trafficking to the spindle, so it is modelled on the assembly part rather than here. annotons: - id: vf_phuz_spindle label: PhuZ spindle centring the phage nucleus participant: selector_type: FAMILY family: preferred_term: PhuZ phage tubulin description: Grounded by representative members; not in PANTHER. representative_members: - preferred_term: PhuZ (Pseudomonas phage 201phi2-1 phage tubulin) term: id: UniProtKB:B3FK34 label: Phage tubulin-like protein - preferred_term: PhuZ (Pseudomonas phage phiKZ phage tubulin) term: id: UniProtKB:Q8SDC3 label: Phage tubulin-like protein function: preferred_term: GTPase activity term: id: GO:0003924 label: GTPase activity description: >- Curated in UniProt. Dynamic instability, and hence GTP hydrolysis, is required for correct positioning. processes: - preferred_term: positive regulation of viral life cycle term: id: GO:1903902 label: positive regulation of viral life cycle description: >- The curated UniProt term for these proteins, retained for that reason, but a broad regulatory wrapper for what the evidence actually establishes: positioning of the compartment by a virus-encoded cytoskeleton. No more specific process term covers that. locations: - preferred_term: host cell cytoplasm term: id: GO:0030430 label: host cell cytoplasm role_description: >- Positions the compartment at midcell by pushing against it with dynamically unstable bipolar filaments. Capsids do migrate from the membrane to the compartment surface for packaging (PMID:28082593, and modelled on the assembly part of this module), but neither reference cited here attributes that trafficking to PhuZ, so no such role is asserted for it. evidence: - source_id: PMID:22726436 title: A phage tubulin assembles dynamic filaments by an atypical mechanism to center viral DNA within the host cell. statement: Establishes the positioning function. supporting_text: >- PhuZ forms a filamentous array that is required for positioning phage DNA within the bacterial cell. - source_id: PMID:22726436 statement: Establishes that filament dynamics, not mere presence, is what is required. supporting_text: >- Correct positioning to the cell center and optimal phage reproduction only occur when the PhuZ filament is dynamic. - source_id: PMID:28082593 statement: >- Grounds the pushing mechanism. PMID:22726436 proposes it explicitly as speculation ("we therefore speculate"); this paper reports it as an observation. supporting_text: >- confirming that these dynamically unstable filaments center phage DNA by a pushing mechanism - source_id: PMID:28082593 statement: >- Grounds the bipolar architecture, which the word "bipolar" appears nowhere in PMID:22726436 to support. supporting_text: >- Centrally positioned GFP-gp105 shells continued to be pushed back and forth by opposing filaments of the bipolar PhuZ spindle, causing them to oscillate near the cell center - order: 3 role: viral transcription within the factory node: id: vf_transcription label: Viral transcription inside the factory module_type: BIOLOGICAL_PROCESS description: >- Transcription occurs at defined sites within the factory, and its products leave. Where the geometry has been resolved - mimivirus and the phage nucleus - transcription is physically separated from translation, which occurs in a ring or zone immediately outside the compartment. That separation is a defining property of the factory rather than an incidental one, and it is the observation the viral eukaryogenesis argument rests on. concepts: - preferred_term: viral transcription term: id: GO:0019083 label: viral transcription evidence: - source_id: PMID:40511921 title: Mimivirus transcription and translation occur at well-defined locations within amoeba host cells. statement: Establishes spatially defined intra-factory transcription and extra-factory translation. supporting_text: >- Although viral mRNA localization changes depend on the infection stage, transcription occurs at well-defined spots within the viral factory. - source_id: PMID:40511921 statement: Establishes the translation ring outside the factory. supporting_text: >- When transported outside of the viral factory, the translation of viral mRNA takes place in a well-defined ring surrounding it. - source_id: PMID:41513996 title: A giant virus forms a specialized subcellular environment within its amoeba host for efficient translation. statement: >- Independent confirmation that the peri-factory zone is a distinct translational environment, not merely where ribosomes happen to be. supporting_text: >- Using in situ labelling, we found that viral mRNAs and newly synthesized proteins were localized in the periphery of the viral factory, suggesting that APMV creates a discrete subcellular environment to facilitate translation. variant_sets: - id: vf_transcriptase_chemistry_axis label: Template chemistry of intra-factory transcription axis: genome template type selection: EXACTLY_ONE variants: - id: vf_dna_templated_transcription label: DNA-templated transcription module_type: REACTION concepts: - preferred_term: DNA-templated viral transcription term: id: GO:0039695 label: DNA-templated viral transcription description: >- Cytoplasmic DNA viruses (poxviruses, Nucleocytoviricota) carry their own multisubunit RNA polymerase into the factory, which is what allows a DNA virus to transcribe outside the nucleus at all. Marseilleviridae are the exception that proves the point: lacking a packaged polymerase, they must recruit the host's. annotons: - id: vf_viral_dna_dependent_rna_polymerase label: Virus-encoded DNA-directed RNA polymerase acting inside the factory participant: selector_type: ANY_WITH_FUNCTION required_function: preferred_term: DNA-directed RNA polymerase activity term: id: GO:0003899 label: DNA-directed RNA polymerase activity function: preferred_term: DNA-directed RNA polymerase activity term: id: GO:0003899 label: DNA-directed RNA polymerase activity processes: - preferred_term: DNA-templated viral transcription term: id: GO:0039695 label: DNA-templated viral transcription locations: - preferred_term: cytoplasmic viral factory term: id: GO:0039714 label: cytoplasmic viral factory role_description: >- Transcribes the viral genome at defined foci inside the factory. Left as an abstract selector: the giant-virus polymerases are poorly represented in reviewed UniProt entries. - id: vf_rna_templated_transcription label: RNA-templated transcription module_type: REACTION concepts: - preferred_term: RNA-templated viral transcription term: id: GO:0039696 label: RNA-templated viral transcription description: >- In Mononegavirales the same L polymerase both transcribes and replicates, switching mode according to the N/P context it meets - which is precisely the context the condensate concentrates. annotons: - id: vf_mononegavirales_l_polymerase label: Mononegavirales large (L) polymerase inside the condensate factory participant: selector_type: FAMILY family: preferred_term: Mononegavirales large structural protein (L) description: Grounded by representative members; not in PANTHER. representative_members: - preferred_term: L (rabies virus large structural protein) term: id: UniProtKB:A3F5L9 label: Large structural protein - preferred_term: L (measles virus RNA-directed RNA polymerase L) term: id: UniProtKB:P12576 label: RNA-directed RNA polymerase L - preferred_term: L (Zaire ebolavirus RNA-directed RNA polymerase L) term: id: UniProtKB:Q05318 label: RNA-directed RNA polymerase L function: preferred_term: RNA-directed RNA polymerase activity term: id: GO:0003968 label: RNA-directed RNA polymerase activity processes: - preferred_term: viral transcription term: id: GO:0019083 label: viral transcription locations: - preferred_term: cytoplasmic viral factory term: id: GO:0039714 label: cytoplasmic viral factory role_description: >- Recruited into the condensate by the phosphoprotein, where it clusters into foci whose spacing changes when replication is switched on. evidence: - source_id: PMID:37443171 statement: >- Establishes that the polymerase is spatially organised within the condensate and that the organisation tracks replication state. supporting_text: >- Within the viral factory, we found the EBOV polymerase clusters into foci. The distance between these foci increases when viral replication is enabled. - order: 4 role: genome replication within the factory node: id: vf_genome_replication label: Viral genome replication inside the factory module_type: BIOLOGICAL_PROCESS description: >- Genome synthesis is the function the compartment exists to accelerate and to hide. Its position within the factory is the best-established fact about coronaviral and flaviviral replication organelles, and the step that phage nucleus formation gates. concepts: - preferred_term: viral genome replication term: id: GO:0019079 label: viral genome replication - preferred_term: viral replication complex term: id: GO:0019034 label: viral replication complex variant_sets: - id: vf_replication_chemistry_axis label: Genome chemistry of intra-factory replication axis: genome type selection: EXACTLY_ONE variants: - id: vf_dna_genome_replication label: DNA genome replication module_type: REACTION concepts: - preferred_term: viral DNA genome replication term: id: GO:0039693 label: viral DNA genome replication annotons: - id: vf_viral_dna_polymerase label: Viral DNA polymerase acting inside the factory participant: selector_type: ANY_WITH_FUNCTION required_function: preferred_term: DNA-directed DNA polymerase activity term: id: GO:0003887 label: DNA-directed DNA polymerase activity function: preferred_term: DNA-directed DNA polymerase activity term: id: GO:0003887 label: DNA-directed DNA polymerase activity processes: - preferred_term: viral DNA genome replication term: id: GO:0039693 label: viral DNA genome replication role_description: >- Replicates the genome within the factory. In vaccinia the ER-derived membranes surrounding early factories coincide with active DNA replication and disperse as the factory shifts to virion assembly, so the boundary and this step are coupled in time. - id: vf_rna_genome_replication label: RNA genome replication module_type: REACTION concepts: - preferred_term: viral RNA genome replication term: id: GO:0039694 label: viral RNA genome replication annotons: - id: vf_viral_rna_polymerase label: Viral RNA-directed RNA polymerase acting inside the factory participant: selector_type: ANY_WITH_FUNCTION required_function: preferred_term: RNA-directed RNA polymerase activity term: id: GO:0003968 label: RNA-directed RNA polymerase activity description: >- Representative members are attached to the concrete boundary variants above (tombusvirus p92, chikungunya P1234) rather than repeated here. function: preferred_term: RNA-directed RNA polymerase activity term: id: GO:0003968 label: RNA-directed RNA polymerase activity processes: - preferred_term: viral RNA genome replication term: id: GO:0039694 label: viral RNA genome replication role_description: >- Synthesises genomic RNA inside the compartment; in membrane-bounded factories it is anchored at the spherule neck or DMV interior, in condensate factories it is concentrated by the scaffold proteins. - order: 5 role: virion assembly and genome packaging node: id: vf_assembly label: Virion assembly and genome packaging at the factory module_type: BIOLOGICAL_PROCESS description: >- The factory's late programme. Where it has been resolved, assembly is spatially ordered: in giant viruses morphogenesis initiates centrally and matures toward the factory periphery; in jumbo phages capsids assemble on the cytoplasmic membrane and dock on the shell surface to be filled. Either way, packaging happens at the boundary, which is why assembly and the boundary cannot be separated into independent modules. concepts: - preferred_term: virion assembly term: id: GO:0019068 label: virion assembly - preferred_term: viral genome packaging term: id: GO:0019072 label: viral genome packaging - preferred_term: host cell viral assembly compartment term: id: GO:0072517 label: host cell viral assembly compartment annotons: - id: vf_capsid_assembly label: Structural protein assembling the capsid within the factory participant: selector_type: ANY_WITH_FUNCTION required_function: preferred_term: structural constituent of virion term: id: GO:0039660 label: structural constituent of virion description: >- Typically the major capsid protein; ASFV p72 is given as an orienting example of an NCLDV double-jelly-roll capsid protein concentrated in the factory. function: preferred_term: structural constituent of virion term: id: GO:0039660 label: structural constituent of virion processes: - preferred_term: viral capsid assembly term: id: GO:0019069 label: viral capsid assembly locations: - preferred_term: host cell viral assembly compartment term: id: GO:0072517 label: host cell viral assembly compartment role_description: >- Concentrated into the factory to near-exclusivity, which is the original observation that motivated the aggresome comparison. evidence: - source_id: PMID:11331297 statement: >- Establishes selective concentration of viral structural proteins and exclusion of host proteins. supporting_text: >- Factories exclude host proteins, suggesting that they are novel subcellular structures induced by viruses. - id: vf_asfv_capsid_example label: ASFV major capsid protein p72 as a factory-assembled structural protein participant: selector_type: GENE_PRODUCT gene_product: preferred_term: African swine fever virus major capsid protein p72 term: id: UniProtKB:P22776 label: Hexon protein p72 function: preferred_term: structural constituent of virion term: id: GO:0039660 label: structural constituent of virion processes: - preferred_term: virion assembly term: id: GO:0019068 label: virion assembly role_description: >- Concrete grounding for the abstract capsid role: supplies roughly a third of virion mass and is almost exclusively localised to the perinuclear factory during infection. - id: vf_genome_packaging_at_boundary label: Genome packaging into preassembled capsids at the factory boundary participant: selector_type: ANY_PARTICIPANT description: >- The packaging apparatus differs by lineage (portal/terminase in phages, vertex-associated machinery in NCLDVs) and is not resolved to a single selector here. processes: - preferred_term: viral genome packaging term: id: GO:0019072 label: viral genome packaging role_description: >- In the phage nucleus the geometry is explicit: capsids assemble outside the compartment, are trafficked to its surface, and are filled there, so the shell is both the container of the genome and the docking surface for packaging. evidence: - source_id: PMID:28082593 statement: Establishes packaging at the compartment surface. supporting_text: >- Later during infection, viral capsids assembled on the cytoplasmic membrane and moved to the surface of the compartment for DNA packaging. - order: 6 role: shielding from host defences node: id: vf_shielding label: Shielding of replication intermediates from host defences module_type: BIOLOGICAL_PROCESS description: >- Compartmentalisation is simultaneously a concentration device and a concealment device, and GO's definition of a viral factory names both. The shielding is a consequence of the boundary rather than a separate machine, which is why this part carries a CAUSES edge from boundary formation rather than sitting in the temporal chain. concepts: - preferred_term: symbiont-mediated evasion of host immune response term: id: GO:0042783 label: symbiont-mediated evasion of host immune response - preferred_term: symbiont-mediated perturbation of host defenses term: id: GO:0030682 label: symbiont-mediated perturbation of host defenses variant_sets: - id: vf_shielding_mechanism_axis label: Shielding mechanism axis: how the boundary excludes the host defence effector selection: ONE_OR_MORE variants: - id: vf_nuclease_exclusion label: Steric exclusion of host nucleases by the protein shell module_type: MODULE description: >- The cleanest demonstration that compartmentalisation alone confers immunity: the phage shell blocks CRISPR-Cas and restriction enzymes without any anti-CRISPR chemistry, and the protection is lost when the nuclease is engineered to enter. The complementary result - sensitivity to RNA-targeting Cas13a, whose substrate leaves the compartment - shows the barrier is spatial rather than biochemical. annotons: - id: vf_chimallin_nuclease_exclusion label: Chimallin shell excluding host CRISPR-Cas and restriction nucleases participant: selector_type: FAMILY family: preferred_term: Chimallin (ChmA) phage nuclear shell protein representative_members: - preferred_term: ChmA (Pseudomonas phage phiKZ chimallin gp54) term: id: UniProtKB:Q8SDA8 label: Chimallin processes: - preferred_term: symbiont-mediated evasion of host restriction-modification system term: id: GO:0099018 label: symbiont-mediated evasion of host restriction-modification system description: >- Covers the restriction-enzyme half of the exclusion. GO's definition illustrates the term with methyltransferases and direct inhibitors, but it is not limited to them, and the repository already reads it that way: genes/9CAUD/darB proposes GO:0099018 for cis-acting physical protection of packaged DNA with no demonstrated methylation. A steric barrier is the same kind of case. The evasion branch is the correct one either way (GO:0099018 is_a GO:0141177, evasion of recognition by a host innate immune effector). - preferred_term: symbiont-mediated suppression of host CRISPR-cas system term: id: GO:0098672 label: symbiont-mediated suppression of host CRISPR-cas system description: >- Retained as the only available CRISPR-facing term, but it misdescribes the mechanism: GO:0098672 is_a GO:0052031 (perturbation of host defense response), and the shell does not perturb the CRISPR-Cas system at all. The system stays intact and is evaded spatially - which is what the paper's own controls show. See the module-level ontology gap for the missing evasion-flavoured CRISPR term. role_description: >- Physically segregates the phage genome from host immunity nucleases for the whole infection. The exclusion is steric, not inhibitory: relocalising EcoRI inside the compartment restores targeting, and RNA-targeting Cas13a remains effective because its substrate leaves the shell. evidence: - source_id: PMID:31819262 title: A bacteriophage nucleus-like compartment shields DNA from CRISPR nucleases. statement: Establishes exclusion of Cas and restriction enzymes by the compartment. supporting_text: >- Cas proteins and restriction enzymes are unable to access the phage DNA throughout the infection, but engineering the relocalization of EcoRI inside the compartment enables targeting of the phage and protection of host cells. - id: vf_membrane_sequestration_of_replication_intermediates label: Membrane sequestration of double-stranded replication intermediates module_type: MODULE description: >- In membrane-bounded factories the double-stranded replication intermediate, the ligand for cytosolic pattern-recognition receptors, sits inside a sealed lumen. This is the most widely invoked - and the least directly demonstrated - shielding mechanism: the dsRNA has been localised inside the vesicles, but the causal link to reduced sensing is usually inferred. annotons: - id: vf_dsrna_sequestration label: Sequestration of the replication intermediate inside the factory lumen participant: selector_type: ANY_PARTICIPANT description: >- The property belongs to the compartment rather than to a single gene product. processes: - preferred_term: symbiont-mediated evasion of host immune response term: id: GO:0042783 label: symbiont-mediated evasion of host immune response locations: - preferred_term: double membrane vesicle viral factory term: id: GO:0039718 label: double membrane vesicle viral factory role_description: >- Keeps the dsRNA replication intermediate out of the cytosol where it would be sensed. evidence: - source_id: PMID:19380115 statement: >- Establishes that the dsRNA intermediate is inside the virus-induced vesicles. supporting_text: >- we detect double-stranded RNA, a presumed marker of RNA replication, inside virus-induced vesicles. - source_id: PMID:24549844 statement: >- States the defence-evasion function of the compartment directly. Quoted in full at module level rather than here, where only a fragment of the sentence is on point. - order: 7 role: egress from the factory optional: true node: id: vf_egress label: Non-lytic egress of progeny virions from the factory module_type: TRANSPORT_STEP description: >- Optional because many infections end in lysis. Where non-lytic egress has been resolved, the route runs through host organelles recruited to the factory: reovirus virions pass from the inclusion into modified, de-acidified lysosome-derived sorting organelles that bud membranous carriers to the plasma membrane. Exocytosis-like release is also inferred for pandoraviruses and cedratviruses from vesicle accumulation in the absence of lysis. annotons: - id: vf_lysosomal_sorting_organelle_egress label: Lysosome-derived sorting organelle carrying virions out of the factory participant: selector_type: ANY_PARTICIPANT description: >- The viral factor directing lysosome recruitment and de-acidification is not identified. locations: - preferred_term: host cell lysosome term: id: GO:0044187 label: host cell lysosome role_description: >- Receives mature virions from the inclusion through membrane-fusion points and delivers them to the plasma membrane in membranous carriers, without lysing the cell. evidence: - source_id: PMID:32356864 title: A modified lysosomal organelle mediates nonlytic egress of reovirus. statement: Establishes a continuous membrane route from the factory to the cell surface. supporting_text: >- ET of VI-SO-MC interfaces demonstrated that these compartments are connected by membrane-fusion points, through which mature virions are transported. - source_id: PMID:32356864 statement: >- Establishes that the organelle is a modified host lysosome, connecting this step to the host-recruitment part, and that the virus de-acidifies it before loading virions. supporting_text: >- Reovirus infection induces an increase in the number and size of lysosomes and modifies the pH of these organelles from ∼4.5-5 to ∼6.1 after recruitment to VIs and before incorporation of virions. - order: 8 role: antagonists of the factory optional: true node: id: vf_antagonists label: Antagonists acting on the assembled factory module_type: REGULATORY_STEP description: >- Two unrelated classes of antagonist converge on the factory as a unit rather than on any individual step: host restriction proteases that accumulate in replication compartments, and virophages that parasitise the giant-virus factory as a replication niche. Grouped as one optional part because both presuppose a fully formed factory. concepts: - preferred_term: negative regulation of viral genome replication term: id: GO:0045071 label: negative regulation of viral genome replication annotons: - id: vf_fam111a_restriction label: Host FAM111A restricting replication in the factory participant: selector_type: GENE_PRODUCT gene_product: preferred_term: human serine protease FAM111A term: id: UniProtKB:Q96PZ2 label: Serine protease FAM111A description: >- Carries GO:0045071 negative regulation of viral genome replication and GO:0008236 serine-type peptidase activity in UniProt. function: preferred_term: serine-type peptidase activity term: id: GO:0008236 label: serine-type peptidase activity processes: - preferred_term: negative regulation of viral genome replication term: id: GO:0045071 label: negative regulation of viral genome replication role_description: >- Host range restriction factor counteracted by the SV40 large T antigen C-terminal region; its proteolytic activity is the presumed but not demonstrated basis of the restriction. evidence: - source_id: PMID:23093934 title: Identification of FAM111A as an SV40 host range restriction and adenovirus helper factor. statement: Establishes FAM111A as a restriction factor targeted by SV40 LT. supporting_text: >- FAM111A functions as a host range restriction factor that is specifically targeted by SV40 LT. - id: vf_fam111b_restriction label: Host FAM111B accumulating in replication compartments participant: selector_type: GENE_PRODUCT gene_product: preferred_term: human serine protease FAM111B term: id: UniProtKB:Q6SJ93 label: Serine protease FAM111B function: preferred_term: serine-type peptidase activity term: id: GO:0008236 label: serine-type peptidase activity processes: - preferred_term: negative regulation of viral genome replication term: id: GO:0045071 label: negative regulation of viral genome replication locations: - preferred_term: replication compartment term: id: GO:0046809 label: replication compartment role_description: >- The paralog that actually restricts murine cytomegalovirus in primate cells, and the clearest case of a host factor localising to the factory itself. Present in primates and absent in rodents, which is why MCMV has no countermeasure for it. evidence: - source_id: PMID:39494906 title: E2F3-dependent activation of FAM111B restricts mouse cytomegalovirus replication in primate cells. statement: Establishes which paralog restricts, against the prior expectation. supporting_text: >- we demonstrated that FAM111B, but not its paralog FAM111A, suppresses MCMV replication in human and rhesus macaque cells. - source_id: PMID:39494906 statement: Establishes localisation to the replication compartment. supporting_text: >- By immunofluorescence, we detected FAM111B predominantly in the nucleus of infected cells with enrichment in viral replication compartments, suggesting that it might play a role during viral replication. - id: vf_virophage_parasitism label: Virophage parasitising the giant-virus factory participant: selector_type: ANY_PARTICIPANT description: >- A small dsDNA virophage, e.g. Sputnik; no reviewed UniProt entry is asserted for its gene products here. locations: - preferred_term: cytoplasmic viral factory term: id: GO:0039714 label: cytoplasmic viral factory role_description: >- Cannot replicate in the amoeba alone and depends on the giant-virus factory as its replication niche, reducing the giant virus's infectious progeny. Evidence that the factory is a resource exploitable by a third party - the strongest functional analogy between a factory and a cellular organelle. evidence: - source_id: PMID:18690211 title: The virophage as a unique parasite of the giant mimivirus. statement: Establishes obligate dependence on the giant-virus factory. supporting_text: >- Sputnik cannot multiply in Acanthamoeba castellanii but grows rapidly, after an eclipse phase, in the giant virus factory found in amoebae co-infected with APMV4. connections: - source: vf_host_recruitment target: vf_boundary connection_type: PROVIDES_INPUT_FOR description: >- Host membranes, lipids, and cytoskeleton supply the material and the position of the boundary. This is the one edge that runs against the part ordering (part 2 feeding part 1): recruitment is continuous rather than a stage, and the parts are ordered by when each becomes the focus of the cycle, not by strict precedence. The five PRECEDES edges carry the temporal ordering. chaining_status: NOT_APPLICABLE chaining_note: Non-metabolic edge; no reaction intermediate to chain. - source: vf_boundary target: vf_transcription connection_type: PRECEDES description: >- The compartment is established before transcription is localised within it. The Chimalliviridae EPI vesicle makes this explicit: early genes are transcribed from within a membrane-bound compartment. chaining_status: NOT_APPLICABLE chaining_note: Ordering of compartment biogenesis before its contents; not a reaction chain. - source: vf_transcription target: vf_genome_replication connection_type: PRECEDES description: >- Early transcription supplies the replication proteins; in Chimalliviridae replication begins only after the genome is transferred from the transcriptionally active EPI vesicle into the phage nucleus. chaining_status: NOT_APPLICABLE chaining_note: Temporal/regulatory ordering, not metabolite continuity. - source: vf_genome_replication target: vf_assembly connection_type: PRECEDES description: Genomes must be synthesised before they are packaged. chaining_status: NOT_APPLICABLE chaining_note: Temporal ordering of the late programme; not a reaction chain. - source: vf_assembly target: vf_egress connection_type: PRECEDES description: Mature virions leave the factory after packaging. chaining_status: NOT_APPLICABLE chaining_note: Temporal ordering; not a reaction chain. - source: vf_boundary target: vf_shielding connection_type: CAUSES description: >- Shielding is a consequence of the boundary, not an independent activity: the same barrier that concentrates the replication machinery excludes the host effectors that would act on it. - source: vf_antagonists target: vf_genome_replication connection_type: NEGATIVELY_REGULATES description: >- Host restriction proteases accumulate in the replication compartment and suppress genome replication there; virophages divert factory output to their own progeny.