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
Autor(es): Lidbury Brett A, Rulli Nestor E, Musso Cristina M, Cossetto Susan B, Zaid Ali, Suhrbier Andreas, Rothenfluh Harald S, Rolph Michael S, Mahalingam Suresh
Resumo: Alphaviruses, such as chikungunya virus, o'nyong-nyong virus, - Ross River virus (RRV), cause outbreaks of human rheumatic disease worldwide. RRV is a positive-sense single-str-ed RNA virus endemic to Australia - 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, - a small-plaque variant (RRV(PERS)) was isolated after several weeks of culture. Nucleotide sequence analysis of RRV(PERS) found several nucleotide differences in the nonstructural protein (nsP) region of the RRV(PERS) genome. A point mutation was also detected in the E2 gene. Compared to the parent virus (RRV-T48), RRV(PERS) showed significantly enhanced resistance to beta interferon (IFN-?)-stimulated antiviral activity. RRV(PERS) infection of RAW 264.7 macrophages induced lower levels of IFN-? expression - production than infection with RRV-T48. RRV(PERS) was also able to inhibit type I IFN signaling. Mice infected with RRV(PERS) exhibited significantly enhanced disease severity - 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 - sensitivity to alpha/beta IFN (IFN-?/?).
Imprenta: Journal of Virology, v. 85, n. 11, p. 5651-5663, 2011
Identificador do objeto digital: 10.1128/JVI.01189-10
Descritores: Chikungunya virus - Cell ; Chikungunya virus - Cytopathology ; Chikungunya virus - Genome ; Chikungunya virus - Immune response ; Chikungunya virus - Pathogenesis ; Chikungunya virus - Proteins ; Chikungunya virus - RNA ; Chikungunya virus - Cytokines ; Chikungunya virus - Immune response ; Chikungunya virus - Viral infections ; Chikungunya Virus - Virus ; Chikungunya virus - Epidemiology ; Chikungunya virus - Immunology ; Chikungunya virus - Public health
Data de publicação: 2011
