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Journal of Virology, July 2002, p. 6435-6441, Vol. 76, No. 13
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.13.6435-6441.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

STAT2 Acts as a Host Range Determinant for Species-Specific Paramyxovirus Interferon Antagonism and Simian Virus 5 Replication

Jean-Patrick Parisien, Joe F. Lau, and Curt M. Horvath*

Immunobiology Center, The Mount Sinai School of Medicine, New York, New York 10029

Received 7 January 2002/ Accepted 24 March 2002

The antiviral state induced by alpha/beta interferon (IFN-{alpha}/ß) is a powerful selective pressure for virus evolution of evasive strategies. The paramyxoviruses simian virus 5 (SV5) and human parainfluenza virus 2 (HPIV2) overcome IFN-{alpha}/ß responses through the actions of their V proteins, which induce proteasomal degradation of cellular IFN-{alpha}/ß-activated signal transducers and activators of transcription STAT1 and STAT2. SV5 infection induces STAT1 degradation and IFN-{alpha}/ß inhibition efficiently in human cells but not in mouse cells, effectively restricting SV5 host range. Here, the cellular basis for this species specificity is demonstrated to result from differences between human and murine STAT2. Expression in mouse cells of full-length or truncated human STAT2 cDNA is sufficient to permit antagonism of endogenous murine IFN-{alpha}/ß signaling by SV5 and HPIV2 V proteins. Furthermore, virus-induced STAT protein degradation is observed in mouse cells only in the presence of ectopically expressed human STAT2. The results indicate that STAT2 acts as an intracellular determinant of paramyxovirus host range restriction, which contributes to the species specificity of virus replication, and that human STAT2 can confer a growth advantage for SV5 in the murine host.

* Corresponding author. Mailing address: Box 1630, East Building Room 12-20D, One Gustave L. Levy Pl., New York, NY 10029. Phone: (212) 659-9406. Fax: (212) 849-2525. E-mail: curt.horvath{at}mssm.edu.

Journal of Virology, July 2002, p. 6435-6441, Vol. 76, No. 13
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.13.6435-6441.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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