Viral factory (virus-induced replication microcompartment)

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.

MODULE:viral_factoryDRAFTABSTRACTOrganelle Lifecyclemodules/viral_factory.yaml
viral factoryGO:0039713 viral replication complex formation and maintenanceGO:0046786 viral replication complexGO:0019034
PMID:42734359
The organization and dynamics of viral factories.
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.
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.
PMID:42734359
Supports modelling the compartment boundary as a variant axis rather than as a fixed property of the module.
Some are enclosed by host-derived membranes, while others exist as biomolecular condensates from liquid-liquid phase separation.
PMID:42734359
Supports a distinct host-recruitment part alongside the viral replication programme.
VFs recruit host lipids, cytoskeletal elements, and metabolic enzymes, effectively reprogramming the intracellular environment to favor viral replication.
GO:0039713
viral factory
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.
PMID:24549844
Reovirus forms neo-organelles for progeny particle assembly within reorganized cell membranes.
Independent statement of the same three-part functional definition used here (concentration, defence evasion, coordinated release), from a dsRNA virus system.
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.

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.

26Nodes
8Parts
6Variant Sets
17Variants
32Annotons
7Connections

Derived QC

Recommended-field compliance

96.9% recommended fields populated
  • knowledge_gaps[0].provenance[1] · supporting_text (0/1)

Module deep research

✗ none found

No MODULE:viral_factory deep-research report alongside the module YAML.

Leaf nodes lacking representative members

✓ representative grounding skipped for abstract module.

Template conformance

✓ every declared conforms_to bundle matches its template motif.

Reaction chaining (advisory)

✓ every PRECEDES step chains, or its break is acknowledged via chaining_status.

  • vf_boundary → vf_transcription [NOT_CHECKED]
    Ordering of compartment biogenesis before its contents; not a reaction chain.
  • vf_transcription → vf_genome_replication [NOT_CHECKED]
    Temporal/regulatory ordering, not metabolite continuity.
  • vf_genome_replication → vf_assembly [NOT_CHECKED]
    Temporal ordering of the late programme; not a reaction chain.
  • vf_assembly → vf_egress [NOT_CHECKED]
    Temporal ordering; not a reaction chain.

Function consistency and core coverage

2 gene-function check(s) reflected in core functions · 0 conflict(s) · 26 evidence or coverage gap(s) (33 comparison(s))

Retained noncore functions are reported separately; they do not require promotion to core functions. Support from representative genes does not establish conservation across the whole family. Missing reviews or identifiers leave a claim unverified.

AnnotonParticipantFunctionAssessment
vf_membrane_remodeling ANY_WITH_FUNCTION
Gene 		membrane bending activity
GO:0180020 		Participant Unchecked
No direct UniProt participant to compare. Abstract selectors and complex-wide activities cannot be inferred from donor or subunit gene reviews.
vf_alphavirus_spherule Chikungunya virus non-structural polyprotein P1234
UniProtKB:Q8JUX6
Gene 		RNA-directed RNA polymerase activity
GO:0003968 		Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
vf_alphavirus_nsp1_membrane_shaping Chikungunya virus mRNA-capping enzyme nsP1
UniProtKB:Q8JUX6
Gene 		membrane bending activity
GO:0180020 		Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
vf_tombusvirus_spherule Tomato bushy stunt virus p92 replicase (and its p33 cleavage product)
UniProtKB:P15962
Gene 		RNA-directed RNA polymerase activity
GO:0003968 		Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
vf_nucleoprotein_condensate_scaffold N (rabies virus nucleoprotein)
UniProtKB:P16285
Family Representative 		molecular condensate scaffold activity
GO:0140693 		Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
vf_nucleoprotein_condensate_scaffold N (measles virus nucleoprotein)
UniProtKB:P04851
Family Representative 		molecular condensate scaffold activity
GO:0140693 		Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
vf_nucleoprotein_condensate_scaffold NP (Zaire ebolavirus nucleoprotein)
UniProtKB:P18272
Family Representative 		molecular condensate scaffold activity
GO:0140693 		Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
vf_phosphoprotein_condensate_partner P (rabies virus phosphoprotein)
UniProtKB:P69479
Family Representative 		molecular condensate scaffold activity
GO:0140693 		Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
vf_phosphoprotein_condensate_partner P (measles virus phosphoprotein)
UniProtKB:P03422
Family Representative 		molecular condensate scaffold activity
GO:0140693 		Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
vf_coronavirus_n_condensate SARS-CoV-2 nucleoprotein N
UniProtKB:P0DTC9
Gene 		molecular condensate scaffold activity
GO:0140693 		Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
vf_poxvirus_h5_condensate Vaccinia virus H5 (OPG110)
UniProtKB:P07242
Gene 		molecular condensate scaffold activity
GO:0140693 		Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
vf_nuclear_condensate_ebna2 Epstein-Barr virus nuclear antigen 2 (EBNA2)
UniProtKB:P12978
Gene 		molecular condensate scaffold activity
GO:0140693 		Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
vf_chimallin_shell ChmA (Pseudomonas phage 201phi2-1 chimallin gp105)
UniProtKB:B3FIW8
Family Representative 		structural molecule activity
GO:0005198 		Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
vf_chimallin_shell ChmA (Pseudomonas phage phiKZ chimallin gp54)
UniProtKB:Q8SDA8
Family Representative 		structural molecule activity
GO:0005198 		Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
vf_vimentin_cage human vimentin
UniProtKB:P08670
Gene 		structural constituent of cytoskeleton
GO:0005200 		Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
vf_pi4k_recruitment human phosphatidylinositol 4-kinase beta (PI4KB)
UniProtKB:Q9UBF8
Gene 		1-phosphatidylinositol 4-kinase activity
GO:0004430 		Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
vf_phuz_spindle PhuZ (Pseudomonas phage 201phi2-1 phage tubulin)
UniProtKB:B3FK34
Family Representative 		GTPase activity
GO:0003924 		Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
vf_phuz_spindle PhuZ (Pseudomonas phage phiKZ phage tubulin)
UniProtKB:Q8SDC3
Family Representative 		GTPase activity
GO:0003924 		Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
vf_viral_dna_dependent_rna_polymerase ANY_WITH_FUNCTION
Gene 		DNA-directed RNA polymerase activity
GO:0003899 		Participant Unchecked
No direct UniProt participant to compare. Abstract selectors and complex-wide activities cannot be inferred from donor or subunit gene reviews.
vf_mononegavirales_l_polymerase L (rabies virus large structural protein)
UniProtKB:A3F5L9
Family Representative 		RNA-directed RNA polymerase activity
GO:0003968 		Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
vf_mononegavirales_l_polymerase L (measles virus RNA-directed RNA polymerase L)
UniProtKB:P12576
Family Representative 		RNA-directed RNA polymerase activity
GO:0003968 		Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
vf_mononegavirales_l_polymerase L (Zaire ebolavirus RNA-directed RNA polymerase L)
UniProtKB:Q05318
Family Representative 		RNA-directed RNA polymerase activity
GO:0003968 		Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
vf_viral_dna_polymerase ANY_WITH_FUNCTION
Gene 		DNA-directed DNA polymerase activity
GO:0003887 		Participant Unchecked
No direct UniProt participant to compare. Abstract selectors and complex-wide activities cannot be inferred from donor or subunit gene reviews.
vf_viral_rna_polymerase ANY_WITH_FUNCTION
Gene 		RNA-directed RNA polymerase activity
GO:0003968 		Participant Unchecked
No direct UniProt participant to compare. Abstract selectors and complex-wide activities cannot be inferred from donor or subunit gene reviews.
vf_capsid_assembly ANY_WITH_FUNCTION
Gene 		structural constituent of virion
GO:0039660 		Participant Unchecked
No direct UniProt participant to compare. Abstract selectors and complex-wide activities cannot be inferred from donor or subunit gene reviews.
vf_asfv_capsid_example African swine fever virus major capsid protein p72
UniProtKB:P22776
Gene 		structural constituent of virion
GO:0039660 		Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
vf_fam111a_restriction human serine protease FAM111A
UniProtKB:Q96PZ2
Gene 		serine-type peptidase activity
GO:0008236 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
vf_fam111b_restriction human serine protease FAM111B
UniProtKB:Q6SJ93
Gene 		serine-type peptidase activity
GO:0008236 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
vf_nucleoprotein_condensate_scaffold Mononegavirales nucleoprotein (N/NP)
Family 		molecular condensate scaffold activity
GO:0140693 		Family Id Missing
The family has no identifier linking it to a curated family review.
vf_phosphoprotein_condensate_partner Mononegavirales phosphoprotein (P)
Family 		molecular condensate scaffold activity
GO:0140693 		Family Id Missing
The family has no identifier linking it to a curated family review.
vf_chimallin_shell Chimallin (ChmA) phage nuclear shell protein
Family 		structural molecule activity
GO:0005198 		Family Id Missing
The family has no identifier linking it to a curated family review.
vf_phuz_spindle PhuZ phage tubulin
Family 		GTPase activity
GO:0003924 		Family Id Missing
The family has no identifier linking it to a curated family review.
vf_mononegavirales_l_polymerase Mononegavirales large structural protein (L)
Family 		RNA-directed RNA polymerase activity
GO:0003968 		Family Id Missing
The family has no identifier linking it to a curated family review.

Feedback loops (advisory, prose-driven: a regulator counts as "feedback" when its own description says so)

✓ every negative regulator described as feedback has an upstream edge closing the loop.

  • vf_antagonists ⊣ vf_genome_replication [input]
    vf_antagonists is a negative regulator with no upstream edge (not described as feedback)

Gene-review completeness (2/26 grounded genes reviewed)

1 complete review(s) · 0 with deep research · 24 missing review · 2 reviewed but lacking deep research

Gene Review Complete Deep research
Rotavirus A SA11 non-structural protein 2 A2T3P0 ✗ — —
Rotavirus A SA11 non-structural protein 5 A2T3Q9 ✗ — —
L (rabies virus large structural protein) A3F5L9 ✗ — —
ChmA (Pseudomonas phage 201phi2-1 chimallin gp105) B3FIW8 ✗ — —
PhuZ (Pseudomonas phage 201phi2-1 phage tubulin) B3FK34 ✗ — —
FAM111A Q96PZ2 ✓ ✓ ✗
FAM111B Q6SJ93 ✓ 16/19 ✗
P (measles virus phosphoprotein) P03422 ✗ — —
N (measles virus nucleoprotein) P04851 ✗ — —
Vaccinia virus H5 (OPG110) P07242 ✗ — —
human vimentin P08670 ✗ — —
SARS-CoV-2 replicase polyprotein 1a (nsp3 pore component) P0DTC1 ✗ — —
SARS-CoV-2 nucleoprotein N P0DTC9 ✗ — —
L (measles virus RNA-directed RNA polymerase L) P12576 ✗ — —
Epstein-Barr virus nuclear antigen 2 (EBNA2) P12978 ✗ — —
Tomato bushy stunt virus p92 replicase (and its p33 cleavage product) P15962 ✗ — —
N (rabies virus nucleoprotein) P16285 ✗ — —
NP (Zaire ebolavirus nucleoprotein) P18272 ✗ — —
Dengue virus 2 genome polyprotein (NS4A/NS4B membrane-remodelling region) P18356 ✗ — —
African swine fever virus major capsid protein p72 P22776 ✗ — —
P (rabies virus phosphoprotein) P69479 ✗ — —
L (Zaire ebolavirus RNA-directed RNA polymerase L) Q05318 ✗ — —
Chikungunya virus non-structural polyprotein P1234 Q8JUX6 ✗ — —
ChmA (Pseudomonas phage phiKZ chimallin gp54) Q8SDA8 ✗ — —
PhuZ (Pseudomonas phage phiKZ phage tubulin) Q8SDC3 ✗ — —
human phosphatidylinositol 4-kinase beta (PI4KB) Q9UBF8 ✗ — —

Details

Context
VirusesNCBITaxon:10239
host cell cytoplasmGO:0030430
productive infection of a host cell compartment boundary mechanism is lineage-specific
Viral factory (virus-induced replication microcompartment)Organelle Lifecycleviral_factory

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.

viral factoryGO:0039713 viral replication complex formation and maintenanceGO:0046786 viral replication complexGO:0019034
Context
VirusesNCBITaxon:10239
host cell cytoplasmGO:0030430
productive infection of a host cell compartment boundary mechanism is lineage-specific

Connections

vf_host_recruitment -> vf_boundary Provides Input For
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.
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.
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.
Genomes must be synthesised before they are packaged.
vf_assembly -> vf_egress Precedes
Mature virions leave the factory after packaging.
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.
vf_antagonists -> vf_genome_replication Negatively Regulates
Host restriction proteases accumulate in the replication compartment and suppress genome replication there; virophages divert factory output to their own progeny.
Part 1: compartment boundary formation
Compartment nucleation and boundary formationCellular Componentvf_boundary

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.

viral factoryGO:0039713
Variant set: Compartment boundary mechanism by physical basis of the compartment boundary (One Or More)

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.

Host-membrane-derived boundaryCellular Componentvf_membrane_boundary

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.

spherule viral factoryGO:0039717 double membrane vesicle viral factoryGO:0039718 tube viral factoryGO:0039719

Annotons

Viral membrane-remodelling protein deforming a host organelle membrane
vf_membrane_remodeling
Participant: Any With Function: membrane bending activity
Required Function:
membrane bending activityGO:0180020
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

membrane bending activityGO:0180020
Targets: host endomembrane donating the factory boundary

Processes

symbiont-mediated perturbation of host membraneGO:0141171

Deforms a donor host membrane into the closed or necked geometry that defines the factory lumen.

PMID:19380115
Composition and three-dimensional architecture of the dengue virus replication and assembly sites.
Establishes an ER-derived, vesicle-and-pore boundary containing the dsRNA replication intermediate.
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.
Double-membrane-spanning export pore of the coronavirus replication organelle
vf_dmv_export_pore
Participant: Gene Product: SARS-CoV-2 replicase polyprotein 1a (nsp3 pore component)
Gene Product:
SARS-CoV-2 replicase polyprotein 1a (nsp3 pore component)UniProtKB:P0DTC1 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.

Processes

double membrane vesicle viral factory assemblyGO:0140526

Locations

double membrane vesicle viral factoryGO:0039718 double membrane vesicle viral factory membraneGO:0062242

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.

PMID:32763915
A molecular pore spans the double membrane of the coronavirus replication organelle.
Establishes the pore and its role in RNA export from the sealed DMV.
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.
PMID:32511245
A unifying structural and functional model of the coronavirus replication organelle: Tracking down RNA synthesis.
Establishes the DMV, rather than any other virus-induced membrane structure, as the site of coronaviral RNA synthesis.
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 set: Host organelle donating the boundary membrane by donor organelle (Exactly One)

The donor is a fixed, lineage-specific choice, which is why this axis is EXACTLY_ONE while the boundary-mechanism axis above is not.

Endoplasmic reticulum / ERGIC-derived boundaryCellular Componentvf_er_ergic_donor

Flaviviruses invaginate the rough ER into vesicle packets and convoluted membranes; coronaviruses derive double-membrane vesicles from the ER-Golgi intermediate compartment.

Context
host cell endoplasmic reticulumGO:0044165 host cell endoplasmic reticulum-Golgi intermediate compartmentGO:0044172

Annotons

Flaviviral polyprotein driving ER invagination
vf_dengue_er_invagination
Participant: Gene Product: Dengue virus 2 genome polyprotein (NS4A/NS4B membrane-remodelling region)
Gene Product:
Dengue virus 2 genome polyprotein (NS4A/NS4B membrane-remodelling region)UniProtKB:P18356

Processes

viral RNA genome replicationGO:0039694

Locations

host cell endoplasmic reticulumGO:0044165

Representative of the flaviviral replication organelle: a single ER-derived network carrying both the replication vesicles and, apposed to their pores, the budding sites.

PMID:19380115
Establishes that the vesicles, convoluted membranes, and budding particles form one ER-derived network.
Electron tomography (ET) shows DENV-induced membrane structures to be part of one ER-derived network.
Plasma-membrane-derived boundaryCellular Componentvf_plasma_membrane_donor

Alphaviruses generate spherules by deforming the host plasma membrane; in chikungunya virus these persist at the plasma membrane rather than being internalised.

Context
host cell plasma membraneGO:0020002

Annotons

Alphaviral non-structural polyprotein forming a plasma-membrane spherule
vf_alphavirus_spherule
Participant: Gene Product: Chikungunya virus non-structural polyprotein P1234
Gene Product:
Chikungunya virus non-structural polyprotein P1234UniProtKB:Q8JUX6 Carries GO:0020002 host cell plasma membrane in UniProt; nsP1 provides the membrane-binding amphipathic anchor and nsP4 the polymerase.

Function

RNA-directed RNA polymerase activityGO:0003968

Processes

viral RNA genome replicationGO:0039694

Locations

host cell plasma membraneGO:0020002

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.

PMID:38940586
In situ fate of Chikungunya virus replication organelles.
Establishes the spherule as the membranous replication organelle housing the replication complex.
Replication of the viral RNA genome occurs in specialized membranous replication organelles (ROs) or spherules, which contain the viral replication complex.
PMID:38940586
Supports persistence and continued growth of the plasma-membrane spherule rather than its internalisation.
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.
Alphaviral nsP1 ring shaping and sealing the spherule neck
vf_alphavirus_nsp1_membrane_shaping
Participant: Gene Product: Chikungunya virus mRNA-capping enzyme nsP1
Gene Product:
Chikungunya virus mRNA-capping enzyme nsP1UniProtKB:Q8JUX6 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

membrane bending activityGO:0180020 Asserted on the amphipathic-insertion mechanism GO:0180020's definition names explicitly. This is a module-level assertion, not a curated UniProt annotation.

Processes

symbiont-mediated perturbation of host membraneGO:0141171

Locations

host cell plasma membraneGO:0020002

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.

PMID:38940586
Establishes the membrane-deforming mechanism as amphipathic insertion, which is one of the mechanisms GO:0180020 is defined over.
which forms amphipathic membrane-binding spikes penetrating by about 10 Å into detergent FC12 micelles
PMID:38940586
Establishes that nsP1 both anchors the replication complex to the bilayer and constitutes the neck structure separating spherule lumen from cytoplasm.
supported the assembly of an nsP1 connecting pore separating the inner part of the spherule from the cytoplasm
Peroxisome-derived boundaryCellular Componentvf_peroxisome_donor

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
host cell peroxisomeGO:0120149

Annotons

Tombusviral replication protein forming a peroxisomal spherule
vf_tombusvirus_spherule
Participant: Gene Product: Tomato bushy stunt virus p92 replicase (and its p33 cleavage product)
Gene Product:
Tomato bushy stunt virus p92 replicase (and its p33 cleavage product)UniProtKB:P15962 p33, the N-terminal product of this ORF, is the membrane-bound spherule-forming protein; p92 is the read-through polymerase.

Function

RNA-directed RNA polymerase activityGO:0003968

Processes

viral RNA genome replicationGO:0039694

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.

PMID:42734359
Source review: places tombusvirus and bromovirus spherules on host peroxisomes and ER respectively.
Biomolecular condensate boundary (liquid-liquid phase separation)Cellular Componentvf_condensate_boundary

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.

viroplasm viral factoryGO:0039716 cytoplasmic viral factoryGO:0039714 nuclear viral factoryGO:0039715

Annotons

Mononegavirales nucleoprotein condensate scaffold
vf_nucleoprotein_condensate_scaffold
Participant: Family: Mononegavirales nucleoprotein (N/NP)
Family:
Mononegavirales nucleoprotein (N/NP) 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: N (rabies virus nucleoprotein)UniProtKB:P16285 N (measles virus nucleoprotein)UniProtKB:P04851 NP (Zaire ebolavirus nucleoprotein)UniProtKB:P18272

Function

molecular condensate scaffold activityGO:0140693

Processes

viral replication complex formation and maintenanceGO:0046786

Locations

cytoplasmic viral factoryGO:0039714

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.

PMID:28680096
Negri bodies are viral factories with properties of liquid organelles.
Establishes the rabies virus factory as a liquid organelle and the N+P pair as sufficient to build it.
Coexpression of rabies virus N and P proteins results in cytoplasmic inclusions recapitulating NBs properties.
PMID:32270045
Measles virus nucleo- and phosphoproteins form liquid-like phase-separated compartments that promote nucleocapsid assembly.
Establishes that the condensate accelerates the reaction it houses - a functional, not merely architectural, role for the boundary.
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.
PMID:37443171
Spatial and functional arrangement of Ebola virus polymerase inside phase-separated viral factories.
Extends the condensate architecture to filoviruses and shows internal spatial organisation within the droplet.
We show that intracellularly reconstituted EBOV viral factories are biomolecular condensates, with composition-dependent internal exchange dynamics that likely facilitates viral replication.
Mononegavirales phosphoprotein condensate partner
vf_phosphoprotein_condensate_partner
Participant: Family: Mononegavirales phosphoprotein (P)
Family:
Mononegavirales phosphoprotein (P) Grounded by representative members only; no PANTHER family covers these proteins.
Representative Members: P (rabies virus phosphoprotein)UniProtKB:P69479 P (measles virus phosphoprotein)UniProtKB:P03422

Function

molecular condensate scaffold activityGO:0140693

Processes

viral transcriptionGO:0019083

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.

PMID:28680096
Identifies the specific P determinants required for condensate formation.
This minimal system reveals that an intrinsically disordered domain and the dimerization domain of P are essential for Negri bodies-like structures formation.
Coronaviral nucleocapsid protein condensate for genome packaging
vf_coronavirus_n_condensate
Participant: Gene Product: SARS-CoV-2 nucleoprotein N
Gene Product:
SARS-CoV-2 nucleoprotein NUniProtKB:P0DTC9 Already carries GO:0140693 molecular condensate scaffold activity and GO:0019074 viral RNA genome packaging in UniProt.

Function

molecular condensate scaffold activityGO:0140693

Processes

viral RNA genome packagingGO:0019074

Locations

host cell cytoplasmGO:0030430

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.

PMID:42734359
Source review: places the SARS-CoV-2 N condensate as a distinct second factory site alongside the DMVs.
Rotavirus NSP2-NSP5 viroplasm condensate
vf_rotavirus_viroplasm_condensate
Participant: Protein Complex: Rotavirus viroplasm-forming NSP2-NSP5 condensate
Protein Complex:
Rotavirus viroplasm-forming NSP2-NSP5 condensate 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:
NSP5 (viroplasm-forming phosphoprotein)
Participant: Gene Product: Rotavirus A SA11 non-structural protein 5
Gene Product:
Rotavirus A SA11 non-structural protein 5UniProtKB:A2T3Q9
Role: Condensate-forming partner whose hyperphosphorylation during late infection hardens the condensate's material properties.
NSP2 (RNA chaperone)
Participant: Gene Product: Rotavirus A SA11 non-structural protein 2
Gene Product:
Rotavirus A SA11 non-structural protein 2UniProtKB:A2T3P0
Role: RNA chaperone partner; brings viral transcripts into the condensate.

Processes

viral genome replicationGO:0019079

Locations

viroplasm viral factoryGO:0039716

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.

PMID:34524703
Liquid-liquid phase separation underpins the formation of replication factories in rotaviruses.
Establishes the NSP5/NSP2 condensate as the rotavirus replication factory.
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.
PMID:34524703
Establishes that the condensate's material state is regulated across the infection cycle.
During late infection, these condensates exhibited altered material properties and became resistant to propylene glycol, coinciding with hyperphosphorylation of NSP5.
Poxviral H5 condensate nucleating the cytoplasmic factory
vf_poxvirus_h5_condensate
Participant: Gene Product: Vaccinia virus H5 (OPG110)
Gene Product:
Vaccinia virus H5 (OPG110)UniProtKB:P07242 Carries GO:0039693 viral DNA genome replication and GO:0019083 viral transcription in UniProt; the condensate-scaffold role is the addition proposed here.

Function

molecular condensate scaffold activityGO:0140693

Processes

viral DNA genome replicationGO:0039693

Locations

host cell cytoplasmGO:0030430

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.

PMID:41264624
Poxvirus H5 mediates the formation of liquid-liquid phase separation condensates which promote virus factory assembly.
Establishes H5-driven LLPS.
Here, we report that H5, a DNA-binding protein of vaccinia virus (VACV) could undergo LLPS through its N-terminal intrinsically disordered region (IDR).
PMID:41264624
Establishes that the condensate is required for factory assembly and productive replication, not merely correlated with it.
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
Nuclear condensate factory of Epstein-Barr virus
vf_nuclear_condensate_ebna2
Participant: Gene Product: Epstein-Barr virus nuclear antigen 2 (EBNA2)
Gene Product:
Epstein-Barr virus nuclear antigen 2 (EBNA2)UniProtKB:P12978

Function

molecular condensate scaffold activityGO:0140693

Locations

nuclear viral factoryGO:0039715

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.

PMID:31941785
Phase Separation of Epstein-Barr Virus EBNA2 and Its Coactivator EBNALP Controls Gene Expression.
Establishes nuclear viral LLPS and its IDR dependence.
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.
Self-assembled proteinaceous shell boundary (phage nucleus)Cellular Componentvf_protein_shell_boundary

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.

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

Chimallin nuclear shell lattice
vf_chimallin_shell
Participant: Family: Chimallin (ChmA) phage nuclear shell protein
Family:
Chimallin (ChmA) phage nuclear shell protein Grounded by representative members; PANTHER does not classify these phage proteins.
Representative Members: ChmA (Pseudomonas phage 201phi2-1 chimallin gp105)UniProtKB:B3FIW8 ChmA (Pseudomonas phage phiKZ chimallin gp54)UniProtKB:Q8SDA8

Function

structural molecule activityGO:0005198 The only available molecular-function grounding; no term expresses "self-assembling compartment shell subunit".

Locations

host cell cytoplasmGO:0030430

Self-assembles as a flexible sheet into a closed micrometre-scale compartment around the replicating phage genome; the sole principal component of the shell.

PMID:35922510
Architecture and self-assembly of the jumbo bacteriophage nuclear shell.
Establishes chimallin as the principal and sufficient shell component.
we show that chimallin self-assembles as a flexible sheet into closed micrometre-scale compartments.
PMID:28082593
Assembly of a nucleus-like structure during viral replication in bacteria.
Establishes functional segregation across the shell: replication and transcription inside, translation outside.
Proteins involved in DNA replication and transcription localized inside the compartment, whereas proteins involved in translation and nucleotide synthesis localized outside.
PMID:37667030
Identification of the bacteriophage nucleus protein interaction network.
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.
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.
Membrane-bound early phage infection vesicle preceding the shell
vf_epi_vesicle_precursor
Participant: Any Participant: 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.
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

DNA-templated viral transcriptionGO:0039695

Locations

host cell cytoplasmGO:0030430

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.

PMID:40168997
Sequential membrane- and protein-bound organelles compartmentalize genomes during phage infection.
Establishes the EPI vesicle as a functional precursor compartment.
Early phage genes are expressed from the EPI vesicle, demonstrating its functionality as a prokaryotic, transcriptionally active, membrane-bound organelle.
PMID:40168997
Establishes the ordering: transfer into the phage nucleus is a precondition for genome replication.
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.
Part 2: host system recruitment
Recruitment and remodelling of host systems around the factoryBiological Processvf_host_recruitment

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.

PMID:42734359
Source review framing for this part.
VFs recruit host lipids, cytoskeletal elements, and metabolic enzymes, effectively reprogramming the intracellular environment to favor viral replication.
Variant set: Recruited host system by host system co-opted by the factory (One Or More)
Intermediate filament cage around the factoryModulevf_intermediate_filament_cage

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

Host vimentin forming the factory cage
vf_vimentin_cage
Participant: Gene Product: human vimentin
Gene Product:
human vimentinUniProtKB:P08670 Host, not viral: this annoton records a host protein recruited by the factory.

Function

structural constituent of cytoskeletonGO:0005200

Locations

intermediate filamentGO:0005882

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.

PMID:11331297
Aggresomes resemble sites specialized for virus assembly.
Establishes the vimentin cage and mitochondrial recruitment as shared between aggresomes and ASFV factories.
Both structures caused rearrangement of intermediate filaments and the collapse of vimentin into characteristic cages, and both recruited mitochondria and cellular chaperones.
Mitochondrial recruitment to the factory peripheryModulevf_mitochondrial_recruitment

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

Directed migration of host mitochondria to the factory
vf_mitochondrion_recruitment
Participant: Any Participant: The viral factor that triggers or targets the migration is unidentified; see the module-level knowledge gap.
The viral factor that triggers or targets the migration is unidentified; see the module-level knowledge gap.

Locations

host cell mitochondrionGO:0033650

Places an ATP source immediately outside the factory boundary during the assembly phase.

PMID:9696857
Migration of mitochondria to viral assembly sites in African swine fever virus-infected cells.
Establishes active, directed recruitment rather than passive co-localisation.
Immunofluorescence microscopy revealed that these accumulations of mitochondria are originated by a massive migration of the organelle to the virus assembly sites.
PMID:9696857
Supports selectivity for assembly-stage factories, the basis for the energetic interpretation.
These clusters surround viral factories that contain assembling particles but not factories where only precursor membranes are seen.
Host lipid-kinase recruitment generating a distinct membrane lipid compositionModulevf_lipid_microenvironment

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

Host phosphatidylinositol 4-kinase generating the PI4P-rich factory membrane
vf_pi4k_recruitment
Participant: Gene Product: human phosphatidylinositol 4-kinase beta (PI4KB)
Gene Product:
human phosphatidylinositol 4-kinase beta (PI4KB)UniProtKB:Q9UBF8

Function

1-phosphatidylinositol 4-kinase activityGO:0004430

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.

PMID:20510927
Viral reorganization of the secretory pathway generates distinct organelles for RNA replication.
Establishes PI4P as functionally required, not merely enriched.
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.
Transient recruitment of host nuclear transcription machineryModulevf_host_transcription_machinery_recruitment

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

Recruitment of host nuclear transcription machinery to the cytoplasmic factory
vf_nuclear_factor_recruitment
Participant: Any Participant: The virion-delivered factor responsible is unidentified; see the module-level knowledge gap.
The virion-delivered factor responsible is unidentified; see the module-level knowledge gap.

Processes

DNA-templated viral transcriptionGO:0039695

Locations

cytoplasmic viral factoryGO:0039714

Supplies the transcription activity the virion does not carry, making an otherwise cytoplasmic replication cycle nucleus-dependent.

PMID:28429720
Noumeavirus replication relies on a transient remote control of the host nucleus.
Establishes the recruitment and its transience.
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.
Phage tubulin spindle positioning the factoryModulevf_phage_spindle_positioning

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

PhuZ spindle centring the phage nucleus
vf_phuz_spindle
Participant: Family: PhuZ phage tubulin
Family:
PhuZ phage tubulin Grounded by representative members; not in PANTHER.
Representative Members: PhuZ (Pseudomonas phage 201phi2-1 phage tubulin)UniProtKB:B3FK34 PhuZ (Pseudomonas phage phiKZ phage tubulin)UniProtKB:Q8SDC3

Function

GTPase activityGO:0003924 Curated in UniProt. Dynamic instability, and hence GTP hydrolysis, is required for correct positioning.

Processes

positive regulation of viral life cycleGO:1903902

Locations

host cell cytoplasmGO:0030430

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.

PMID:22726436
A phage tubulin assembles dynamic filaments by an atypical mechanism to center viral DNA within the host cell.
Establishes the positioning function.
PhuZ forms a filamentous array that is required for positioning phage DNA within the bacterial cell.
PMID:22726436
Establishes that filament dynamics, not mere presence, is what is required.
Correct positioning to the cell center and optimal phage reproduction only occur when the PhuZ filament is dynamic.
PMID:28082593
Grounds the pushing mechanism. PMID:22726436 proposes it explicitly as speculation ("we therefore speculate"); this paper reports it as an observation.
confirming that these dynamically unstable filaments center phage DNA by a pushing mechanism
PMID:28082593
Grounds the bipolar architecture, which the word "bipolar" appears nowhere in PMID:22726436 to support.
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
Part 3: viral transcription within the factory
Viral transcription inside the factoryBiological Processvf_transcription

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.

viral transcriptionGO:0019083
PMID:40511921
Mimivirus transcription and translation occur at well-defined locations within amoeba host cells.
Establishes spatially defined intra-factory transcription and extra-factory translation.
Although viral mRNA localization changes depend on the infection stage, transcription occurs at well-defined spots within the viral factory.
PMID:40511921
Establishes the translation ring outside the factory.
When transported outside of the viral factory, the translation of viral mRNA takes place in a well-defined ring surrounding it.
PMID:41513996
A giant virus forms a specialized subcellular environment within its amoeba host for efficient translation.
Independent confirmation that the peri-factory zone is a distinct translational environment, not merely where ribosomes happen to be.
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 set: Template chemistry of intra-factory transcription by genome template type (Exactly One)
DNA-templated transcriptionReactionvf_dna_templated_transcription

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.

DNA-templated viral transcriptionGO:0039695

Annotons

Virus-encoded DNA-directed RNA polymerase acting inside the factory
vf_viral_dna_dependent_rna_polymerase
Participant: Any With Function: DNA-directed RNA polymerase activity
Required Function:
DNA-directed RNA polymerase activityGO:0003899

Function

DNA-directed RNA polymerase activityGO:0003899

Processes

DNA-templated viral transcriptionGO:0039695

Locations

cytoplasmic viral factoryGO:0039714

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.

RNA-templated transcriptionReactionvf_rna_templated_transcription

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.

RNA-templated viral transcriptionGO:0039696

Annotons

Mononegavirales large (L) polymerase inside the condensate factory
vf_mononegavirales_l_polymerase
Participant: Family: Mononegavirales large structural protein (L)
Family:
Mononegavirales large structural protein (L) Grounded by representative members; not in PANTHER.
Representative Members: L (rabies virus large structural protein)UniProtKB:A3F5L9 L (measles virus RNA-directed RNA polymerase L)UniProtKB:P12576 L (Zaire ebolavirus RNA-directed RNA polymerase L)UniProtKB:Q05318

Function

RNA-directed RNA polymerase activityGO:0003968

Processes

viral transcriptionGO:0019083

Locations

cytoplasmic viral factoryGO:0039714

Recruited into the condensate by the phosphoprotein, where it clusters into foci whose spacing changes when replication is switched on.

PMID:37443171
Establishes that the polymerase is spatially organised within the condensate and that the organisation tracks replication state.
Within the viral factory, we found the EBOV polymerase clusters into foci. The distance between these foci increases when viral replication is enabled.
Part 4: genome replication within the factory
Viral genome replication inside the factoryBiological Processvf_genome_replication

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.

viral genome replicationGO:0019079 viral replication complexGO:0019034
Variant set: Genome chemistry of intra-factory replication by genome type (Exactly One)
DNA genome replicationReactionvf_dna_genome_replication
viral DNA genome replicationGO:0039693

Annotons

Viral DNA polymerase acting inside the factory
vf_viral_dna_polymerase
Participant: Any With Function: DNA-directed DNA polymerase activity
Required Function:
DNA-directed DNA polymerase activityGO:0003887

Function

DNA-directed DNA polymerase activityGO:0003887

Processes

viral DNA genome replicationGO:0039693

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.

RNA genome replicationReactionvf_rna_genome_replication
viral RNA genome replicationGO:0039694

Annotons

Viral RNA-directed RNA polymerase acting inside the factory
vf_viral_rna_polymerase
Participant: Any With Function: RNA-directed RNA polymerase activity
Required Function:
RNA-directed RNA polymerase activityGO:0003968
Representative members are attached to the concrete boundary variants above (tombusvirus p92, chikungunya P1234) rather than repeated here.

Function

RNA-directed RNA polymerase activityGO:0003968

Processes

viral RNA genome replicationGO:0039694

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.

Part 5: virion assembly and genome packaging
Virion assembly and genome packaging at the factoryBiological Processvf_assembly

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.

virion assemblyGO:0019068 viral genome packagingGO:0019072 host cell viral assembly compartmentGO:0072517

Annotons

Structural protein assembling the capsid within the factory
vf_capsid_assembly
Participant: Any With Function: structural constituent of virion
Required Function:
structural constituent of virionGO:0039660
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

structural constituent of virionGO:0039660

Processes

viral capsid assemblyGO:0019069

Locations

host cell viral assembly compartmentGO:0072517

Concentrated into the factory to near-exclusivity, which is the original observation that motivated the aggresome comparison.

PMID:11331297
Establishes selective concentration of viral structural proteins and exclusion of host proteins.
Factories exclude host proteins, suggesting that they are novel subcellular structures induced by viruses.
ASFV major capsid protein p72 as a factory-assembled structural protein
vf_asfv_capsid_example
Participant: Gene Product: African swine fever virus major capsid protein p72
Gene Product:
African swine fever virus major capsid protein p72UniProtKB:P22776

Function

structural constituent of virionGO:0039660

Processes

virion assemblyGO:0019068

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.

Genome packaging into preassembled capsids at the factory boundary
vf_genome_packaging_at_boundary
Participant: Any Participant: The packaging apparatus differs by lineage (portal/terminase in phages, vertex-associated machinery in NCLDVs) and is not resolved to a single selector here.
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

viral genome packagingGO:0019072

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.

PMID:28082593
Establishes packaging at the compartment surface.
Later during infection, viral capsids assembled on the cytoplasmic membrane and moved to the surface of the compartment for DNA packaging.
Part 6: shielding from host defences
Shielding of replication intermediates from host defencesBiological Processvf_shielding

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.

symbiont-mediated evasion of host immune responseGO:0042783 symbiont-mediated perturbation of host defensesGO:0030682
Variant set: Shielding mechanism by how the boundary excludes the host defence effector (One Or More)
Steric exclusion of host nucleases by the protein shellModulevf_nuclease_exclusion

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

Chimallin shell excluding host CRISPR-Cas and restriction nucleases
vf_chimallin_nuclease_exclusion
Participant: Family: Chimallin (ChmA) phage nuclear shell protein
Family:
Chimallin (ChmA) phage nuclear shell protein
Representative Members: ChmA (Pseudomonas phage phiKZ chimallin gp54)UniProtKB:Q8SDA8

Processes

symbiont-mediated evasion of host restriction-modification systemGO:0099018 symbiont-mediated suppression of host CRISPR-cas systemGO:0098672

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.

PMID:31819262
A bacteriophage nucleus-like compartment shields DNA from CRISPR nucleases.
Establishes exclusion of Cas and restriction enzymes by the compartment.
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.
Membrane sequestration of double-stranded replication intermediatesModulevf_membrane_sequestration_of_replication_intermediates

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

Sequestration of the replication intermediate inside the factory lumen
vf_dsrna_sequestration
Participant: Any Participant: The property belongs to the compartment rather than to a single gene product.
The property belongs to the compartment rather than to a single gene product.

Processes

symbiont-mediated evasion of host immune responseGO:0042783

Locations

double membrane vesicle viral factoryGO:0039718

Keeps the dsRNA replication intermediate out of the cytosol where it would be sensed.

PMID:19380115
Establishes that the dsRNA intermediate is inside the virus-induced vesicles.
we detect double-stranded RNA, a presumed marker of RNA replication, inside virus-induced vesicles.
PMID:24549844
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.
Part 7: egress from the factory (optional)
Non-lytic egress of progeny virions from the factoryTransport Stepvf_egress

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

Lysosome-derived sorting organelle carrying virions out of the factory
vf_lysosomal_sorting_organelle_egress
Participant: Any Participant: The viral factor directing lysosome recruitment and de-acidification is not identified.
The viral factor directing lysosome recruitment and de-acidification is not identified.

Locations

host cell lysosomeGO:0044187

Receives mature virions from the inclusion through membrane-fusion points and delivers them to the plasma membrane in membranous carriers, without lysing the cell.

PMID:32356864
A modified lysosomal organelle mediates nonlytic egress of reovirus.
Establishes a continuous membrane route from the factory to the cell surface.
ET of VI-SO-MC interfaces demonstrated that these compartments are connected by membrane-fusion points, through which mature virions are transported.
PMID:32356864
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.
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.
Part 8: antagonists of the factory (optional)
Antagonists acting on the assembled factoryRegulatory Stepvf_antagonists

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.

negative regulation of viral genome replicationGO:0045071

Annotons

Host FAM111A restricting replication in the factory
vf_fam111a_restriction
Participant: Gene Product: human serine protease FAM111A
Gene Product:
human serine protease FAM111AUniProtKB:Q96PZ2 Carries GO:0045071 negative regulation of viral genome replication and GO:0008236 serine-type peptidase activity in UniProt.

Function

serine-type peptidase activityGO:0008236

Processes

negative regulation of viral genome replicationGO:0045071

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.

PMID:23093934
Identification of FAM111A as an SV40 host range restriction and adenovirus helper factor.
Establishes FAM111A as a restriction factor targeted by SV40 LT.
FAM111A functions as a host range restriction factor that is specifically targeted by SV40 LT.
Host FAM111B accumulating in replication compartments
vf_fam111b_restriction
Participant: Gene Product: human serine protease FAM111B
Gene Product:
human serine protease FAM111BUniProtKB:Q6SJ93

Function

serine-type peptidase activityGO:0008236

Processes

negative regulation of viral genome replicationGO:0045071

Locations

replication compartmentGO:0046809

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.

PMID:39494906
E2F3-dependent activation of FAM111B restricts mouse cytomegalovirus replication in primate cells.
Establishes which paralog restricts, against the prior expectation.
we demonstrated that FAM111B, but not its paralog FAM111A, suppresses MCMV replication in human and rhesus macaque cells.
PMID:39494906
Establishes localisation to the replication compartment.
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.
Virophage parasitising the giant-virus factory
vf_virophage_parasitism
Participant: Any Participant: A small dsDNA virophage, e.g. Sputnik; no reviewed UniProt entry is asserted for its gene products here.
A small dsDNA virophage, e.g. Sputnik; no reviewed UniProt entry is asserted for its gene products here.

Locations

cytoplasmic viral factoryGO:0039714

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.

PMID:18690211
The virophage as a unique parasite of the giant mimivirus.
Establishes obligate dependence on the giant-virus factory.
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.