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Journal of Virology, November 2003, p. 11555-11562, Vol. 77, No. 21
0022-538X/03/$08.00+0 DOI: 10.1128/JVI.77.21.11555-11562.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.
Expression of the Zinc-Finger Antiviral Protein Inhibits Alphavirus Replication
Matthew J. Bick,1 John-William N. Carroll,1 Guangxia Gao,2 Stephen P. Goff,3 Charles M. Rice,1 and Margaret R. MacDonald1*
Laboratory of Virology and Infectious Diseases, The Rockefeller University, New York, New York 10021,1
Institute of Microbiology, Chinese Academy of Sciences, Beijing 100080, People's Republic of China,2
Department of Biochemistry and Molecular Biophysics, Howard Hughes Medical Institute, Columbia University College of Physicians and Surgeons, New York, New York 100323
Received 16 June 2003/
Accepted 31 July 2003
The rat zinc-finger antiviral protein (ZAP) was recently identified as a host protein conferring resistance to retroviral infection. We analyzed ZAP's ability to inhibit viruses from other families and found that ZAP potently inhibits the replication of multiple members of the Alphavirus genus within the Togaviridae, including Sindbis virus, Semliki Forest virus, Ross River virus, and Venezuelan equine encephalitis virus. However, expression of ZAP did not induce a broad-spectrum antiviral state as some viruses, including vesicular stomatitis virus, poliovirus, yellow fever virus, and herpes simplex virus type 1, replicated to normal levels in ZAP-expressing cells. We determined that ZAP expression inhibits Sindbis virus replication after virus penetration and entry, but before the amplification of newly synthesized plus strand genomic RNA. Using a temperature-sensitive Sindbis virus mutant expressing luciferase, we further showed that translation of incoming viral RNA is blocked by ZAP expression. Elucidation of the antiviral mechanism by which ZAP inhibits Sindbis virus translation may lead to the development of agents with broad activity against alphaviruses.
* Corresponding author. Mailing address: Laboratory of Virology and Infectious Diseases, The Rockefeller University, 1230 York Ave., New York, NY 10021. Phone: (212) 327-7078. Fax: (212) 327-7048. E-mail: macdonm{at}mail.rockefeller.edu.
Journal of Virology, November 2003, p. 11555-11562, Vol. 77, No. 21
0022-538X/03/$08.00+0 DOI: 10.1128/JVI.77.21.11555-11562.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.
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Copyright © 2003 by the American Society for Microbiology. All rights reserved.