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-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.
MeSH Terms
Cell Line
DNA-Binding Proteins/analysis,antagonists & inhibitors
Humans
Interferon-alpha/antagonists & inhibitors
Interferon-beta/antagonists & inhibitors
Respiratory Syncytial Virus Infections/immunology
Respiratory Syncytial Virus, Human/physiology
STAT2 Transcription Factor
Signal Transduction
Trans-Activators/analysis,antagonists & inhibitors
Viral Nonstructural Proteins/physiology
Chemicals
DNA-Binding Proteins
Interferon-alpha
STAT2 Transcription Factor
STAT2 protein, human
Trans-Activators
Viral Nonstructural Proteins
Interferon-beta
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Lo Mindy S
Department of Medicine, Washington University School of Medicine, Campus Box 8052, 660 South Euclid Avenue, St. Louis, MO 63110, USA.
Brazas Robert M
Holtzman Michael J
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