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Journal of Virology, February 2002, p. 1206-1212, Vol. 76, No. 3
0022-538X/01/$04.00+0     DOI: 10.1128/JVI.76.3.1206-1212.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Effects of Influenza A Virus NS1 Protein on Protein Expression: the NS1 Protein Enhances Translation and Is Not Required for Shutoff of Host Protein Synthesis

Mirella Salvatore,1 Christopher F. Basler,1 Jean-Patrick Parisien,2 Curt M. Horvath,2 Svetlana Bourmakina,1 Hongyong Zheng,1 Thomas Muster,3 Peter Palese,1 and Adolfo García-Sastre1*

Department of Microbiology,1 Immunobiology Center, Mount Sinai School of Medicine, New York, New York 10029,2 Department of Dermatology, University of Vienna Medical School, 1090 Vienna, Austria3

Received 18 June 2001/ Accepted 24 October 2001

The influenza A virus NS1 protein, a virus-encoded alpha/beta interferon (IFN-{alpha}/ß) antagonist, appears to be a key regulator of protein expression in infected cells. We now show that NS1 protein expression results in enhancement of reporter gene activity from transfected plasmids. This effect appears to be mediated at the translational level, and it is reminiscent of the activity of the adenoviral virus-associated I (VAI) RNA, a known inhibitor of the antiviral, IFN-induced, PKR protein. To study the effects of the NS1 protein on viral and cellular protein synthesis during influenza A virus infection, we used recombinant influenza viruses lacking the NS1 gene (delNS1) or expressing truncated NS1 proteins. Our results demonstrate that the NS1 protein is required for efficient viral protein synthesis in COS-7 cells. This activity maps to the amino-terminal domain of the NS1 protein, since cells infected with wild-type virus or with a mutant virus expressing a truncated NS1 protein—lacking approximately half of its carboxy-terminal end—showed similar kinetics of viral and cellular protein expression. Interestingly, no major differences in host cell protein synthesis shutoff or in viral protein expression were found among NS1 mutant viruses in Vero cells. Thus, another viral component(s) different from the NS1 protein is responsible for the inhibition of host protein synthesis during viral infection. In contrast to the earlier proposal suggesting that the NS1 protein regulates the levels of spliced M2 mRNA, no effects on M2 protein accumulation were seen in Vero cells infected with delNS1 virus.

* Corresponding author. Mailing address: Department of Microbiology, Mount Sinai School of Medicine, Box 1124, One Gustave L. Levy Pl., New York, NY 10029. Phone: (212) 241-7769. Fax (212) 534-1684. E-mail: adolfo.garcia-sastre{at}mssm.edu.

Journal of Virology, February 2002, p. 1206-1212, Vol. 76, No. 3
0022-538X/01/$04.00+0     DOI: 10.1128/JVI.76.3.1206-1212.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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