Identification 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 Interferon

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Title Identification 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 Interferon
Author Lidbury, Brett A.; Rulli, Nestor; Musso, Cristina M.; Cossetto, Susan B.; Zaid, Ali; Suhrbier, Andreas; Rothenfluh, Harald S.; Rolph, Michael; Mahalingam, Suresh
Journal Name Journal of Virology
Year Published 2011
Place of publication United States
Publisher American Society for Microbiology
Abstract Alphaviruses, 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-β)-stimulated antiviral activity. RRVPERS infection of RAW 264.7 macrophages induced lower levels of IFN-β expression 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-α/β).
Peer Reviewed Yes
Published Yes
Alternative URI http://dx.doi.org/10.1128/JVI.01189-10
Volume 85
Issue Number 11
Page from 5651
Page to 5663
ISSN 0022-538X
Date Accessioned 2012-03-05; 2012-03-09T05:45:37Z
Research Centre Institute for Glycomics
Faculty Faculty of Science, Environment, Engineering and Technology
Subject Biological Sciences
URI http://hdl.handle.net/10072/43517
Publication Type Journal Articles (Refereed Article)
Publication Type Code c1

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