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Journal of Virology, April 2009, p. 3734-3742, Vol. 83, No. 8
0022-538X/09/$08.00+0     doi:10.1128/JVI.02434-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Human Respiratory Syncytial Virus Nonstructural Protein NS2 Antagonizes the Activation of Beta Interferon Transcription by Interacting with RIG-I{triangledown}

Zhenhua Ling, Kim C. Tran, and Michael N. Teng*

Department of Biochemistry and Molecular Biology, Center for Molecular Immunology and Infectious Diseases, Pennsylvania State University, University Park, Pennsylvania 16802

Received 25 November 2008/ Accepted 27 January 2009

A wide variety of RNA viruses have been shown to produce proteins that inhibit interferon (IFN) production and signaling. For human respiratory syncytial virus (RSV), the nonstructural NS1 and NS2 proteins have been shown to block IFN signaling by causing the proteasomal degradation of STAT2. In addition, recombinant RSVs lacking either NS1 or NS2 induce more IFN production than wild-type (wt) RSV in infected cells. However, the mechanisms by which the NS proteins perform this function are unknown. In this study, we focused on defining the mechanism by which NS2 inhibits the induction of IFN transcription. We find that NS2 is required for the early inhibition of IFN transcription since the infection of cells with NS2-deletion RSV resulted in a higher level of IRF3 activation at early time points postinfection compared with that of wt or NS1-deletion RSV infection. In addition, NS2 expression inhibits IFN transcription induced by both the RIG-I and TLR3 pathways. Furthermore, we show that NS2 inhibits RIG-I-mediated IFN promoter activation by binding to the N-terminal CARD of RIG-I and inhibiting its interaction with the downstream component MAVS (IPS-1, VISA, Cardif). Thus, the RSV NS2 protein is a multifunctional IFN antagonist that targets specific components of both the IFN induction and IFN signaling pathways.

* Corresponding author. Mailing address: Department of Biochemistry and Molecular Biology, Pennsylvania State University, 406 Althouse, University Park, PA 16802. Phone: (814) 867-2299. Fax: (814) 863-7024. E-mail: MNT2{at}psu.edu

{triangledown} Published ahead of print on 4 February 2009.

Journal of Virology, April 2009, p. 3734-3742, Vol. 83, No. 8
0022-538X/09/$08.00+0     doi:10.1128/JVI.02434-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Swedan, S., Musiyenko, A., Barik, S. (2009). Respiratory Syncytial Virus Nonstructural Proteins Decrease Levels of Multiple Members of the Cellular Interferon Pathways. J. Virol. 83: 9682-9693 [Abstract] [Full Text]  
  • Scagnolari, C., Midulla, F., Pierangeli, A., Moretti, C., Bonci, E., Berardi, R., De Angelis, D., Selvaggi, C., Di Marco, P., Girardi, E., Antonelli, G. (2009). Gene Expression of Nucleic Acid-Sensing Pattern Recognition Receptors in Children Hospitalized for Respiratory Syncytial Virus-Associated Acute Bronchiolitis. CVI 16: 816-823 [Abstract] [Full Text]  


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