dc.contributor.author | Liu, Xiang | |
dc.contributor.author | Mutso, Margit | |
dc.contributor.author | Cherkashchenko, Liubov | |
dc.contributor.author | Zusinaite, Eva | |
dc.contributor.author | Herrero, Lara J | |
dc.contributor.author | Doggett, Stephen L | |
dc.contributor.author | Haniotis, John | |
dc.contributor.author | Merits, Andres | |
dc.contributor.author | Herring, Belinda L | |
dc.contributor.author | Taylor, Adam | |
dc.contributor.author | Mahalingam, Suresh | |
dc.date.accessioned | 2020-08-26T03:33:40Z | |
dc.date.available | 2020-08-26T03:33:40Z | |
dc.date.issued | 2020 | |
dc.identifier.issn | 0022-538X | |
dc.identifier.doi | 10.1128/JVI.01788-19 | |
dc.identifier.uri | http://hdl.handle.net/10072/396784 | |
dc.description.abstract | Ross 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.peerreviewed | Yes | |
dc.language | English | |
dc.language.iso | eng | |
dc.publisher | American Society for Microbiology | |
dc.relation.ispartofpagefrom | e01788-19 | |
dc.relation.ispartofissue | 8 | |
dc.relation.ispartofjournal | Journal of Virology | |
dc.relation.ispartofvolume | 94 | |
dc.relation.uri | http://purl.org/au-research/grants/NHMRC/APP1031024 | |
dc.relation.grantID | APP1031024 | |
dc.relation.funders | NHMRC | |
dc.subject.fieldofresearch | Biological sciences | |
dc.subject.fieldofresearch | Agricultural, veterinary and food sciences | |
dc.subject.fieldofresearch | Biomedical and clinical sciences | |
dc.subject.fieldofresearchcode | 31 | |
dc.subject.fieldofresearchcode | 30 | |
dc.subject.fieldofresearchcode | 32 | |
dc.subject.keywords | Science & Technology | |
dc.subject.keywords | Life Sciences & Biomedicine | |
dc.subject.keywords | Virology | |
dc.subject.keywords | Ross River virus | |
dc.subject.keywords | alphavirus | |
dc.title | Identification of Natural Molecular Determinants of Ross River Virus Type I Interferon Modulation | |
dc.type | Journal article | |
dc.type.description | C1 - Articles | |
dcterms.bibliographicCitation | Liu, 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.dateAccepted | 2020-01-24 | |
dc.date.updated | 2020-08-26T03:26:05Z | |
dc.description.version | Version 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.hasfulltext | Full Text | |
gro.griffith.author | Herrero, Lara J. | |
gro.griffith.author | Mahalingam, Suresh | |
gro.griffith.author | Liu, Xiang | |
gro.griffith.author | Mutso, Margit | |