Respiratory syncytial virus nonstructural proteins NS1 and NS2 mediate inhibition of Stat2 expression and alpha/beta interferon responsiveness

MS Lo, RM Brazas, MJ Holtzman - Journal of virology, 2005 - Am Soc Microbiol
MS Lo, RM Brazas, MJ Holtzman
Journal of virology, 2005Am Soc Microbiol
Respiratory syncytial virus (RSV) subverts the antiviral interferon (IFN) response, but the
mechanism for this evasion was unclear. Here we show that RSV preferentially inhibits IFN-
α/β signaling by expression of viral NS1 and NS2. Thus, RSV infection or expression of
recombinant NS1 and NS2 in epithelial host cells causes a marked decrease in Stat2 levels
and the consequent downstream IFN-α/β response. Similarly, NS1/NS2-deficient RSV no
longer decreases Stat2 levels or IFN responsiveness. RSV infection decreased human but …
Abstract
Respiratory syncytial virus (RSV) subverts the antiviral interferon (IFN) response, but the mechanism for this evasion was unclear. Here we show that RSV preferentially inhibits IFN-α/β signaling by expression of viral NS1 and NS2. Thus, RSV infection or expression of recombinant NS1 and NS2 in epithelial host cells causes a marked decrease in Stat2 levels and the consequent downstream IFN-α/β response. Similarly, NS1/NS2-deficient RSV no longer decreases Stat2 levels or IFN responsiveness. RSV infection decreased human but not mouse Stat2 levels, so this mechanism of IFN antagonism may contribute to viral host range, as well as immune subversion.
American Society for Microbiology