title: The immune evasion function of J and Beilong virus V proteins is distinct from that of other paramyxoviruses, consistent with their inclusion in the proposed genus Jeilongvirus.
abstract: IFN-antagonist function is a major determinant of pathogenicity and cross-species infection by viruses, but remains poorly defined for many potentially zoonotic viruses resident in animal species. The paramyxovirus family contains several zoonotic viruses, including highly pathogenic viruses such as Nipah virus and Hendra virus, and an increasing number of largely uncharacterized animal viruses. Here, we report the characterization of IFN antagonism by the rodent viruses J virus (JPV) and Beilong virus (BeiPV) of the proposed genus Jeilongvirus of the paramyxoviruses. Infection of cells by JPV and BeiPV was found to inhibit IFN-activated nuclear translocation of signal transducer and activator of transcription 1 (STAT1). However, in contrast to most other paramyxoviruses, the JPV and BeiPV V proteins did not interact with or inhibit signalling by STAT1 or STAT2, suggesting that JPV/BeiPV use an atypical V protein-independent strategy to target STATs, consistent with their inclusion in a separate genus. Nevertheless, the V proteins of both viruses interacted with melanoma differentiation-associated protein 5 (MDA5) and robustly inhibited MDA5-dependent activation of the IFN-β promoter. This supports a growing body of evidence that MDA5 is a universal target of paramyxovirus V proteins, such that the V-MDA5 interaction represents a potential target for broad-spectrum antiviral approaches.
authors.affiliation: Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria 3800, Australia.
authors.forename: Michelle D
authors.initials: MD
authors.lastname: Audsley
authors.affiliation: CSIRO Health and Biosecurity, Australian Animal Health Laboratory (AAHL), Geelong, Victoria 3220, Australia.
authors.forename: Glenn A
authors.initials: GA
authors.lastname: Marsh
authors.affiliation: Department of Biochemistry and Molecular Biology, BIO21 Molecular Science and Biotechnology Institute, University of Melbourne, Victoria 3010, Australia.
authors.forename: Kim G
authors.initials: KG
authors.lastname: Lieu
authors.affiliation: CSIRO Health and Biosecurity, Australian Animal Health Laboratory (AAHL), Geelong, Victoria 3220, Australia.
authors.forename: Mary
authors.initials: M
authors.lastname: Tachedjian
authors.affiliation: CSIRO Health and Biosecurity, Australian Animal Health Laboratory (AAHL), Geelong, Victoria 3220, Australia.
authors.forename: D Albert
authors.initials: DA
authors.lastname: Joubert
authors.affiliation: CSIRO Health and Biosecurity, Australian Animal Health Laboratory (AAHL), Geelong, Victoria 3220, Australia.|Program in Emerging Infectious Diseases, Duke-NUS Graduate Medical School, 169857Singapore.
authors.forename: Lin-Fa
authors.initials: LF
authors.lastname: Wang
authors.affiliation: Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria 3800, Australia.
authors.forename: David A
authors.initials: DA
authors.lastname: Jans
authors.affiliation: Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria 3800, Australia.|Department of Biochemistry and Molecular Biology, BIO21 Molecular Science and Biotechnology Institute, University of Melbourne, Victoria 3010, Australia.
authors.forename: Gregory W
authors.initials: GW
authors.lastname: Moseley
mesh_terms: D000818:Animals; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000276:immunology; D057809:HEK293 Cells; D006801:Humans; D057131:Immune Evasion; D000072640:Interferon-Induced Helicase, IFIH1; D016898:Interferon-alpha / Q000235:genetics / Q000276:immunology; D018184:Paramyxoviridae Infections / Q000235:genetics / Q000276:immunology* / Q000821:virology; D018098:Paramyxovirinae / Q000145:classification / Q000235:genetics / Q000276:immunology*; D050794:STAT1 Transcription Factor / Q000235:genetics / Q000276:immunology; D050795:STAT2 Transcription Factor / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology*
chemical_list: D016898:Interferon-alpha; D050794:STAT1 Transcription Factor; D050795:STAT2 Transcription Factor; C502891:V protein, Paramyxovirus; D014764:Viral Proteins; C452815:IFIH1 protein, human; D053487:DEAD-box RNA Helicases; D000072640:Interferon-Induced Helicase, IFIH1