Show simple item record

dc.contributor.authorA. Lidbury, Bretten_US
dc.contributor.authorRulli, Nestoren_US
dc.contributor.authorM. Musso, Cristinaen_US
dc.contributor.authorB. Cossetto, Susanen_US
dc.contributor.authorZaid, Alien_US
dc.contributor.authorSuhrbier, Andreasen_US
dc.contributor.authorS. Rothenfluh, Haralden_US
dc.contributor.authorRolph, Michaelen_US
dc.contributor.authorMahalingam, Sureshen_US
dc.description.abstractAlphaviruses, such as chikungunya virus, o'nyong-nyong virus, and Ross River virus (RRV), cause outbreaks of human rheumatic disease worldwide. RRV is a positive-sense single-stranded RNA virus endemic to Australia and Papua New Guinea. In this study, we sought to establish an in vitro model of RRV evolution in response to cellular antiviral defense mechanisms. RRV was able to establish persistent infection in activated macrophages, and a small-plaque variant (RRVPERS) was isolated after several weeks of culture. Nucleotide sequence analysis of RRVPERS found several nucleotide differences in the nonstructural protein (nsP) region of the RRVPERS genome. A point mutation was also detected in the E2 gene. Compared to the parent virus (RRV-T48), RRVPERS showed significantly enhanced resistance to beta interferon (IFN-ߩ-stimulated antiviral activity. RRVPERS infection of RAW 264.7 macrophages induced lower levels of IFN-ߠexpression and production than infection with RRV-T48. RRVPERS was also able to inhibit type I IFN signaling. Mice infected with RRVPERS exhibited significantly enhanced disease severity and mortality compared to mice infected with RRV-T48. These results provide strong evidence that the cellular antiviral response can direct selective pressure for viral sequence evolution that impacts on virus fitness and sensitivity to alpha/beta IFN (IFN-a/ߩ.en_US
dc.publisherAmerican Society for Microbiologyen_US
dc.publisher.placeUnited Statesen_US
dc.relation.ispartofjournalJournal of Virologyen_US
dc.subject.fieldofresearchBiological Sciences not elsewhere classifieden_US
dc.titleIdentification and Characterization of a Ross River Virus Variant That Grows Persistently in Macrophages, Shows Altered Disease Kinetics in a Mouse Model, and Exhibits Resistance to Type I Interferonen_US
dc.typeJournal articleen_US
dc.type.descriptionC1 - Peer Reviewed (HERDC)en_US
dc.type.codeC - Journal Articlesen_US
gro.hasfulltextNo Full Text

Files in this item


There are no files associated with this item.

This item appears in the following Collection(s)

  • Journal articles
    Contains articles published by Griffith authors in scholarly journals.

Show simple item record