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Fix branch 'suppression by virus of host gene expression' >> change labels to 'symbiont-mediated'... #26747

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pgaudet opened this issue Jan 10, 2024 · 9 comments
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@pgaudet
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pgaudet commented Jan 10, 2024

  • 'suppression by virus of host gene expression' >> host transcription shut-off
    & children
  • 'suppression by virus of host mRNA processing'
  • 'suppression by virus of host transcription'
  • 'suppression by virus of host mRNA transcription via inhibition of RNA polymerase II activity'
  • 'suppression by virus of host transcription initiation from RNA polymerase II promoter' >> PMID: 21178485
  • 'induction by virus of catabolism of host mRNA' >> symbiont-mediated degradation of host mRNA

note that these processes probably only occur in viruses; can add a note in the definition

@genegodbold If you have references, please add

@pgaudet pgaudet self-assigned this Jan 10, 2024
@genegodbold
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genegodbold commented Jan 15, 2024

Bacteria messing with host translation

  • Burkholderia lethal factor 1 (BLF1) from Burkholderia pseudomallei: BLF1 deamidates glutamine339 of host eIF4A (eukaryotic initiation factor 4A). This inactivates RNA helicase activity required to unwind secondary structure of mRNA, which in turn, leads to inhibition of protein synthesis in human cells [PMID:22817745].
  • Cholix toxin from Vibrio cholera: Cholix toxin transfers an ADP-ribose moiety from NAD to the eukaryotic ribosomal elongation factor 2 (EF-2), preventing translation from that ribosome [PMID:25494717].
  • LegK4 from Legionella pneumophila: LegK4 is an effector kinase of Legionella that phosphorylates host cytosolic protein chaperone Hsp70 on Thr495 within its substrate-binding domain. Phosphorylation inhibits its ATPase activity and also its ability to fold proteins. This results in a global inhibition of translation [PMID:30827827].
  • Substrate of Icm/Dot I (SidI; lpg2504) from Legionella pneumophila: SidI inhibits protein translation both in vitro and in cells infected with L. pneumophila. SidI binds host elongation factors eEF1A and also eEF1Bgamma. As little as 30 ng SidI was able to block translation in an in vitro system. The following SidI mutants, when expressed in yeast, were not toxic: Glu482Lys, Arg453Leu and Arg453Pro. They weren't completely devoid of the ability to inhibit protein synthesis as indicated by the in vitro translation system [PMID:19386084].

Bacteria messing with host transcription

  • LegAS4 (RomA; lpp1683) from Legionella pneumophila: LegAS4/RomA is a T4SS nucleomodulin effector that contains a eukaryotic SET domain involved in methyltransferase reactions to the epsilon amino group of lysine residues. RomA methylates host histone H3 at Lys14 which leads to transcriptional repression, and this is required for efficient intracellular replication of the bacterium [PMID:23601102].
  • Listeria nuclear targeted protein A (LntA; lmo0438) from Listeria monocytogenes: LntA is a nucleomodulin that targets the host chromatin represor BAHD1 (UniProtQ8TBE0) which can act to silence interferon stimulated genes (ISGs). Cells infected with a listeria mutant lacking LntA derepress interferon stimulated genes through BAHD1 in those cells resulting in less of an immune response [PMID21252314].
  • Outer surface protein F (OspF) from Shigella: OspF dephosphorylates mitogen-activated protein kinases in the nucleus, thereby preventing histone H3 phosphorylation at Ser10 in a gene-specific way. This OspF activity enables shigellae to block the activation of a subset of NFkappaB-responsive genes, leading to compromised recruitment of polymorphonuclear leukocytes to infected tissues [PMID:17159983]. Nuclear translocation of OspF is preceded by conjugation with host SUMO [PMID:27994213]. When OspF is ectopically expressed moves to the cell nucleus and, along with OspB, down-regulates the production of the host cytokine IL-8, perhaps through an association with the host retinoblastoma protein. Cells infected with a mutant Shigella that lacks OspB and OspF attract greater interest in neutrophils which is presumably the result of increased IL-8 production. Deletion of both caused greater IL-8 secretion than the single-deletion mutants [PMID19017275].
  • Rv1988 from Mycobacterium tuberculosis: Rv1988 is a nucleomodulin that acts as a methyltransferase that localizes to the host nucleus and methylates host histone H3 on Arg42 to repress genes involved in the defense against mycobacteria [PMID:26568365].

@genegodbold
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genegodbold commented Jan 15, 2024

Viruses messing with host translation

  • BGLF5 from Epstein-Barr virus: BGLF5 is a viral alkaline nuclease that promotes the localization of the cellular polyA-binding protein (PABPC) to the nucleus. PABPC normally functions to enhance mRNA stability in the cytoplasm. The depletion of cytoplasmic PABPC is expected to impair the stability of cellular transcripts that have reached the cytoplasm [PMID:19468299]. BGLF5 can degrade cellular and viral mRNAs regardless of whether they are polyadenylated to "shutoff" protein translation [PMID:22696660]. BGLF5 induces host translation shutoff by degradation of host mRNAs. Expression of BGLF5 in insect Sf9 cells is sufficient to globally reduce synthesis of new polypeptide chains compared to controls. One of the consequences of translational shutoff is a block in the synthesis of HLA-I and HLA-II and a resulting diminution of antigen-presenting complexes at the surface of infected cells [PMID:17360652].
  • C3L (P3L; VARVgp023) from Variola orthopoxvirus: C3L/P3L inhibits phosphorylation of host elongation initiator factor-2alpha by protein kinase R (PKR). C3L/P3L resembles the eIF2alpha protein that functions in both the inhibition of cellular translation and the inhibition of programmed cell death (apoptosis). eIF2alpha homologs are found in many orthopoxviruses [PMID:16375715].
  • C7 (interferon antagonist; C7; host range protein 2) from Vaccinia orthopoxvirus: C7 acts as a viral determinant for replication in human cells. It inhibits phosphorylation of eukaryotic translation initiation factor 2, thereby inhibiting the shutdown of host cell translation [PMID:19708815].
  • Infected cell protein 34.5 (ICP34.5) from Human herpesvirus 1 ICP34.5 includes a GADD34 homology region that allows the phosphorylation of host eIF2alpha to be abrogated via recruitment of host protein phosphatase-1alpha. This prevents premature shutoff of protein synthesis in HHV-1 infected human cells [PMID:8523596]. ICP34.5 interacts with host eIF2alpha through residues 233-248 [PMID:21622569].
  • Zinc-finger protein (Z protein) from Lymphocytic choriomeningitis mammarenavirus: In cell culture, the Z protein of LCMV associates with host eukaryotic initiation factor 4E and selectively represses translation [PMID:10708446].
  • double-stranded RNA binding protein (dsRNA BP; F3L) from monkeypox virus: The dsRNA-binding protein F3L binds viral dsRNA and thereby blocks activation of host protein kinase R and the host 2'5'-oligoadenylate synthetases (OAS) which shut down host translation in response to host interferon [PMID:12543935].

Viruses messing with host transcription

  • Capsid protein from eastern equine encephalitis virus: The EEEV capsid protein strongly inhibits the expression of host RNA polymerase II-transcribed genes hence reducing host cell RNA and promoting phosphorylation of the eukaryotic initiation factor 2alpha (eIF2alpha) subunit. This suggests capsid-mediated effects upon translation as well. The capsid protein possesses serine protease activity which allows the protein to release itself from the nascent structural polyprotein chain into the cytoplasm during translation [PMID:17267491].
  • Matrix protein (M) from Vesicular stomatitis virus: The matrix protein of VSV is the most abundant in the virus. It is found in the cytoplasm and sometimes linked to the plasma membrane. It inhibits host cellular transcription by associating with the TFIID complex of host RNA polymerase II [PMID:9733895]-[PMID:8985359]. M protein inhibits the transport of host mRNAs out of the nucleus by associating with host NUP98 [PMID:11046154]-[PMID:12351648]. The M protein mutation Asp52Gly suppresses host interferon responses by inhibiting transcription and this is separable from its effects on NFkappaB [PMID:32838932].
  • E6 from Alphapapillomavirus: E6 coordinates the repression of transcription to downregulate expression of STAT1, IFIT1, MX1, TLR3, RIG-I and MDA5 [PMID:21849431]. This is mediated through epigenetic silencing of interferon-kappa [PMID:19887612].
  • Epstein-Barr nuclear antigen 1 (EBNA1) from Epstein-Barr virus: EBNA1 modulates the alternative splicing of host mRNAs in a manner that is not dependent on EBNA1 binding to mRNA [PMID:30832682].

@genegodbold
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There are SO many of these with SO many mechanisms.

@pgaudet
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pgaudet commented Jan 16, 2024

GO:0019056 'modulation by virus of host transcription' >> obsolete, replace by symbiont-mediated perturbation of host transcription

All annotations will be automatically replaced, see geneontology/go-annotation#4931

@pgaudet
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pgaudet commented Jan 16, 2024

Obsolete 'GO:0046778 modification by virus of host mRNA processing': no annotations, no mappings. Unnecessary grouping class.

@pgaudet
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pgaudet commented Jan 16, 2024

obsolete 'GO:0046783 modification by virus of host polysomes' >> same process as GO:0141130 symbiont-mediated inactivation of host ribosome
No annotations, no mappings

@pgaudet
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pgaudet commented Jan 16, 2024

Obsolete modulation by symbiont of host translation
No annotations, no references, no mappings
same as symbiont-mediated perturbation of host translation (was: modulation by virus of host translation)

Obsolete negative regulation by symbiont of host translation
same as symbiont-mediated suppression of host translation
2 CACAO

@pgaudet
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pgaudet commented Jan 16, 2024

Dear all

The proposal has been made to obsolete the following viral or symbiont terms:

  • GO:0046778 modification by virus of host mRNA processing': no annotations, no mappings. Unnecessary grouping class.
  • GO:0046783 modification by virus of host polysomes >> replace by GO:0141130 symbiont-mediated inactivation of host ribosome
  • GO:0019056 modulation by virus of host transcription >> replace by GO:0052026 symbiont-mediated perturbation of host transcription
  • GO:0044073 modulation by symbiont of host translation >> replace by GO:0019057 symbiont-mediated perturbation of host translation
  • GO:0044074 negative regulation by symbiont of host translation >> replace by GO:0039604 symbiont-mediated suppression of host translation
  • GO:0042786 evasion of host immune response via modulation of host antigen processing and presentation>> replace by GO:0039588 suppression by virus of host antigen processing and presentation
  • GO:0052064 symbiont-mediated activation of reactive oxygen species production in host cell >> no replacement; process does not exist

There are 18 annotations to these terms, that will be automatically replaced, except for CACAO annotations, see
geneontology/go-annotation#4934

There are no mappings; these terms are not in any subsets.

You can comment on the ticket: #26747

Thanks, Pascale

@pgaudet
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pgaudet commented Jan 24, 2024

Another reference for symbiont-mediated degradation of host mRNA from @genegodbold

Viral host shutoff protein (Vhs, UL41) from HHV-1: UL41 is an endoribonuclease that cuts host mRNA and thereby shuts off host cell protein translation [PMID12163576][PMID16477041]. UL41 selectively targets cyclic GMP-AMP synthase (cGAS) mRNA for destruction.

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