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Henipaviruses and lyssaviruses target nucleolar treacle protein and regulate ribosomal RNA synthesis
journal contributionposted on 2023-02-20, 04:36 authored by SM Rawlinson, T Zhao, K Ardipradja, Y Zhang, PF Veugelers, JA Harper, CT David, Vinod SundaramoorthyVinod Sundaramoorthy, GW Moseley
The nucleolus is a common target of viruses and viral proteins, but for many viruses the functional outcomes and significance of this targeting remains unresolved. Recently, the first intranucleolar function of a protein of a cytoplasmically-replicating negative-sense RNA virus (NSV) was identified, with the finding that the matrix (M) protein of Hendra virus (HeV) (genus Henipavirus, family Paramyxoviridae) interacts with Treacle protein within nucleolar subcompartments and mimics a cellular mechanism of the nucleolar DNA-damage response (DDR) to suppress ribosomal RNA (rRNA) synthesis. Whether other viruses utilise this mechanism has not been examined. We report that sub-nucleolar Treacle targeting and modulation is conserved between M proteins of multiple Henipaviruses, including Nipah virus and other potentially zoonotic viruses. Furthermore, this function is also evident for P3 protein of rabies virus, the prototype virus of a different RNA virus family (Rhabdoviridae), with Treacle depletion in cells also found to impact virus production. These data indicate that unrelated proteins of viruses from different families have independently developed nucleolar/Treacle targeting function, but that modulation of Treacle has distinct effects on infection. Thus, subversion of Treacle may be an important process in infection by diverse NSVs, and so could provide novel targets for antiviral approaches with broad specificity.
Publication classificationC1 Refereed article in a scholarly journal
Science & TechnologyLife Sciences & BiomedicineCell Biologyhenipavirusmatrixnucleusnucleolusphosphoproteinprotein traffickingrabiesribosome biogenesistreaclevirusTCOF1 GENE-PRODUCTC-TERMINAL DOMAINVIRUS P-PROTEINNUCLEAR-LOCALIZATIONTRANSCRIPTIONIMPORTBATSHUBInfectious DiseasesEmerging Infectious DiseasesVaccine RelatedPreventionBiodefenseGeneticsInfection3 Good Health and Well BeingBiochemistry and Cell Biology not elsewhere classifiedMedical Microbiology not elsewhere classified