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

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...

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Detalles Bibliográficos
Autores principales: Lidbury, Brett A., Rulli, Néstor E., Musso, Cristina M., Cossetto, Susan B., Zaid, Ali, Suhrbier, Andreas, Rothenfluh, Harald S., Rolph, Michael S., Mahalingam, Suresh
Formato: Articulo
Lenguaje:Inglés
Publicado: 2011
Materias:
Ciencias Exactas
Biología
Ross River virus
Alphaviruses
Macrophages
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/84146
Aporte de:
SEDICI (UNLP) de Universidad Nacional de La Plata
id I19-R120-10915-84146
record_format dspace
institution Universidad Nacional de La Plata
institution_str I-19
repository_str R-120
collection SEDICI (UNLP)
language Inglés
topic Ciencias Exactas
Biología
Ross River virus
Alphaviruses
Macrophages
spellingShingle Ciencias Exactas
Biología
Ross River virus
Alphaviruses
Macrophages
Lidbury, Brett A.
Rulli, Néstor E.
Musso, Cristina M.
Cossetto, Susan B.
Zaid, Ali
Suhrbier, Andreas
Rothenfluh, Harald S.
Rolph, Michael S.
Mahalingam, Suresh
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
topic_facet Ciencias Exactas
Biología
Ross River virus
Alphaviruses
Macrophages
description 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 (RRV<sub>PERS</sub>) was isolated after several weeks of culture. Nucleotide sequence analysis of RRV <sub>PERS</sub> found several nucleotide differences in the nonstructural protein (nsP) region of the RRV <sub>PERS</sub> genome. A point mutation was also detected in the E2 gene. Compared to the parent virus (RRV-T48), RRV <sub>PERS</sub> showed significantly enhanced resistance to beta interferon (IFN-β)-stimulated antiviral activity. RRV <sub>PERS</sub> infection of RAW 264.7 macrophages induced lower levels of IFN-β expression and production than infection with RRV-T48. RRV <sub>PERS</sub> was also able to inhibit type I IFN signaling. Mice infected with RRV <sub>PERS</sub> 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).
format Articulo
Articulo
author Lidbury, Brett A.
Rulli, Néstor E.
Musso, Cristina M.
Cossetto, Susan B.
Zaid, Ali
Suhrbier, Andreas
Rothenfluh, Harald S.
Rolph, Michael S.
Mahalingam, Suresh
author_facet Lidbury, Brett A.
Rulli, Néstor E.
Musso, Cristina M.
Cossetto, Susan B.
Zaid, Ali
Suhrbier, Andreas
Rothenfluh, Harald S.
Rolph, Michael S.
Mahalingam, Suresh
author_sort Lidbury, Brett A.
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
title_short 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_sort 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
publishDate 2011
url http://sedici.unlp.edu.ar/handle/10915/84146
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