Respiratory syncytial virus nonstructural proteins NS1 and NS2 mediate inhibition of Stat2 expression and alpha/beta interferon responsiveness.
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-alpha/beta 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-alpha/beta 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.
Department of Medicine, Washington University School of Medicine, Campus Box 8052, 660 South Euclid Avenue, St. Louis, MO 63110, USA.
Mindy S
MS
Lo
Robert M
RM
Brazas
Michael J
MJ
Holtzman
D002460:Cell Line; D004268:DNA-Binding Proteins / Q000032:analysis / Q000037:antagonists & inhibitors*; D006801:Humans; D016898:Interferon-alpha / Q000037:antagonists & inhibitors*; D016899:Interferon-beta / Q000037:antagonists & inhibitors*; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology; D018113:Respiratory Syncytial Virus, Human / Q000502:physiology*; D050795:STAT2 Transcription Factor; D015398:Signal Transduction; D015534:Trans-Activators / Q000032:analysis / Q000037:antagonists & inhibitors*; D017361:Viral Nonstructural Proteins / Q000502:physiology*
D004268:DNA-Binding Proteins; D016898:Interferon-alpha; D050795:STAT2 Transcription Factor; C494084:STAT2 protein, human; D015534:Trans-Activators; D017361:Viral Nonstructural Proteins; D016899:Interferon-beta