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dc.contributor.authorLiu, Xiang
dc.contributor.authorMutso, Margit
dc.contributor.authorCherkashchenko, Liubov
dc.contributor.authorZusinaite, Eva
dc.contributor.authorHerrero, Lara J
dc.contributor.authorDoggett, Stephen L
dc.contributor.authorHaniotis, John
dc.contributor.authorMerits, Andres
dc.contributor.authorHerring, Belinda L
dc.contributor.authorTaylor, Adam
dc.contributor.authorMahalingam, Suresh
dc.date.accessioned2020-08-26T03:33:40Z
dc.date.available2020-08-26T03:33:40Z
dc.date.issued2020
dc.identifier.issn0022-538X
dc.identifier.doi10.1128/JVI.01788-19
dc.identifier.urihttp://hdl.handle.net/10072/396784
dc.description.abstractRoss River virus (RRV) belongs to the genus Alphavirus and is prevalent in Australia. RRV infection can cause arthritic symptoms in patients and may include rash, fever, arthralgia, and myalgia. Type I interferons (IFN) are the primary antiviral cytokines and trigger activation of the host innate immune system to suppress the replication of invading viruses. Alphaviruses are able to subvert the type I IFN system, but the mechanisms used are ill defined. In this study, seven RRV field strains were analyzed for induction of and sensitivity to type I IFN. The sensitivities of these strains to human IFN-β varied significantly and were highest for the RRV 2548 strain. Compared to prototype laboratory strain RRV-T48, RRV 2548 also induced higher type I IFN levels both in vitro and in vivo and caused milder disease. To identify the determinants involved in type I IFN modulation, the region encoding the nonstructural proteins (nsPs) of RRV 2548 was sequenced, and 42 amino acid differences from RRV-T48 were identified. Using fragment swapping and site-directed mutagenesis, we discovered that substitutions E402A and R522Q in nsP1 as well as Q619R in nsP2 were responsible for increased sensitivity of RRV 2548 to type I IFN. In contrast, substitutions A31T, N219T, S580L, and Q619R in nsP2 led to induction of higher levels of type I IFN. With exception of E402A, all these variations are common for naturally occurring RRV strains. However, they are different from all known determinants of type I IFN modulation reported previously in nsPs of alphaviruses.
dc.description.peerreviewedYes
dc.languageEnglish
dc.language.isoeng
dc.publisherAmerican Society for Microbiology
dc.relation.ispartofpagefrome01788-19
dc.relation.ispartofissue8
dc.relation.ispartofjournalJournal of Virology
dc.relation.ispartofvolume94
dc.relation.urihttp://purl.org/au-research/grants/NHMRC/APP1031024
dc.relation.grantIDAPP1031024
dc.relation.fundersNHMRC
dc.subject.fieldofresearchBiological sciences
dc.subject.fieldofresearchAgricultural, veterinary and food sciences
dc.subject.fieldofresearchBiomedical and clinical sciences
dc.subject.fieldofresearchcode31
dc.subject.fieldofresearchcode30
dc.subject.fieldofresearchcode32
dc.subject.keywordsScience & Technology
dc.subject.keywordsLife Sciences & Biomedicine
dc.subject.keywordsVirology
dc.subject.keywordsRoss River virus
dc.subject.keywordsalphavirus
dc.titleIdentification of Natural Molecular Determinants of Ross River Virus Type I Interferon Modulation
dc.typeJournal article
dc.type.descriptionC1 - Articles
dcterms.bibliographicCitationLiu, X; Mutso, M; Cherkashchenko, L; Zusinaite, E; Herrero, LJ; Doggett, SL; Haniotis, J; Merits, A; Herring, BL; Taylor, A; Mahalingam, S, Identification of Natural Molecular Determinants of Ross River Virus Type I Interferon Modulation, Journal of Virology, 2020, 94 (8), pp. e01788-19
dcterms.dateAccepted2020-01-24
dc.date.updated2020-08-26T03:26:05Z
dc.description.versionVersion of Record (VoR)
gro.rights.copyright© 2020 American Society for Microbiology. This is the author-manuscript version of this paper. Reproduced in accordance with the copyright policy of the publisher. Please refer to the journal's website for access to the definitive, published version.
gro.hasfulltextFull Text
gro.griffith.authorHerrero, Lara J.
gro.griffith.authorMahalingam, Suresh
gro.griffith.authorLiu, Xiang
gro.griffith.authorMutso, Margit


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