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Journal of Virology, May 2008, p. 4688-4696, Vol. 82, No. 10
0022-538X/08/$08.00+0     doi:10.1128/JVI.02763-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Expression of Gamma Interferon-Dependent Genes Is Blocked Independently by Virion Host Shutoff RNase and by US3 Protein Kinase {triangledown}

Li Liang and Bernard Roizman*

Marjorie B. Kovler Viral Oncology Laboratories, The University of Chicago, 910 East 58th Street, Chicago, Illinois 60637

Received 30 December 2007/ Accepted 28 February 2008

Gamma interferon receptor {alpha} (IFN-{gamma}R{alpha}) is stable but posttranslationally modified in herpes simplex virus 1(F) [HSV-1(F)]-infected cells. Studies with antibody directed to the phosphorylation site indicate that IFN-{gamma}R{alpha} is phosphorylated by the US3 kinase. The modification is abolished in cells infected with {Delta}US3, {Delta}UL13, or {Delta}(US3/UL13) mutant virus. Transcripts of the IFN-{gamma}-dependent genes do not accumulate in cells transduced with the US3 protein kinase and treated with IFN-{gamma}. In contrast, the accumulation of IFN-{gamma}-dependent gene transcripts is suppressed in cells infected with the wild-type virus, in cells infected with the {Delta}US3 mutant virus, and to a lesser extent in the {Delta}UL41 virus-infected cells. The accumulation of IFN-{gamma}-dependent gene transcripts in {Delta}UL41-infected cells could be due at least in part to a significant delay and reduction in the accumulation of the US3 protein. The results suggest that the expression of IFN-{gamma}-dependent genes is blocked independently by the degradation of IFN-{gamma}-dependent gene transcripts—a function of the virion host shutoff RNase—and by posttranslational modification of the IFN-{gamma}R{alpha} protein.


* Corresponding author. Mailing address: The Marjorie B. Kovler Viral Oncology Laboratories, The University of Chicago, 910 East 58th Street, Chicago, IL 60637. Phone: (773) 702-1898. Fax: (773) 702-1631. E-mail: bernard.roizman{at}bsd.uchicago.edu

{triangledown} Published ahead of print on 5 March 2008.


Journal of Virology, May 2008, p. 4688-4696, Vol. 82, No. 10
0022-538X/08/$08.00+0     doi:10.1128/JVI.02763-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.




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