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Journal of Virology, July 2005, p. 9315-9319, Vol. 79, No. 14
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.14.9315-9319.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Respiratory Syncytial Virus Nonstructural Proteins NS1 and NS2 Mediate Inhibition of Stat2 Expression and Alpha/Beta Interferon Responsiveness

Mindy S. Lo,1 Robert M. Brazas,2,{dagger} and Michael J. Holtzman1,3*

Departments of Medicine,1 Cell Biology, Washington University School of Medicine, St. Louis, Missouri 63110,3 Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina 277102

Received 3 March 2005/ Accepted 28 March 2005

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}/ß 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}/ß 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.

* Corresponding author. Mailing address: Washington University School of Medicine, Campus Box 8052, 660 South Euclid Avenue, St. Louis, MO 63110. Phone: (314) 362-8970. Fax: (314) 362-8987. E-mail: holtzman{at}im.wustl.edu.

{dagger} Present address: Mirus Bio Corporation, Madison, WI 53719.

Journal of Virology, July 2005, p. 9315-9319, Vol. 79, No. 14
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.14.9315-9319.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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