Expression of the zinc-finger antiviral protein inhibits alphavirus replication.
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.
Bick
Matthew J
MJ
Laboratory of Virology and Infectious Diseases, The Rockefeller University, New York, New York 10021, USA.
Carroll
John-William N
JW
Gao
Guangxia
G
Goff
Stephen P
SP
Rice
Charles M
CM
MacDonald
Margaret R
MR
D000524:Alphavirus / Q000145:classification / Q000502:physiology*; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism* / Q000494:pharmacology; D002460:Cell Line; D002522:Chlorocebus aethiops; D006224:Cricetinae; D014176:Protein Biosynthesis; D012367:RNA, Viral / Q000378:metabolism; D016601:RNA-Binding Proteins; D051381:Rats; D012845:Sindbis Virus / Q000502:physiology; D014709:Vero Cells; D014779:Virus Replication; D016335:Zinc Fingers
D002352:Carrier Proteins; D012367:RNA, Viral; D016601:RNA-Binding Proteins; C465959:Zc3hav1 protein, rat