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Journal of Virology, February 2004, p. 1675-1684, Vol. 78, No. 4
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.4.1675-1684.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

The Herpes Simplex Virus ICP0 RING Finger Domain Inhibits IRF3- and IRF7-Mediated Activation of Interferon-Stimulated Genes

Rongtuan Lin,1 Ryan S. Noyce,2 Susan E. Collins,3 Roger D. Everett,4 and Karen L. Mossman2,3*

Lady Davis Research Institute, Montreal H3T 1E2, Canada,1 Departments of Biochemistry,2 Pathology & Molecular Medicine, McMaster University, Hamilton L8N 3Z5, Canada,3 MRC Virology Unit, Glasgow G11 5JR, Scotland, United Kingdom4

Received 14 July 2003/ Accepted 21 October 2003

Virus infection induces a rapid cellular response in cells characterized by the induction of interferon. While interferon itself does not induce an antiviral response, it activates a number of interferon-stimulated genes that collectively function to inhibit virus replication and spread. Previously, we and others reported that herpes simplex virus type 1 (HSV-1) induces an interferon -independent antiviral response in the absence of virus replication. Here, we report that the HSV-1 proteins ICP0 and vhs function in concert to disable the host antiviral response. In particular, we show that ICP0 blocks interferon regulatory factor IRF3- and IRF7-mediated activation of interferon-stimulated genes and that the RING finger domain of ICP0 is essential for this activity. Furthermore, we demonstrate that HSV-1 modifies the IRF3 pathway in a manner different from that of the small RNA viruses most commonly studied.

* Corresponding author. Mailing address: Department of Pathology & Molecular Medicine and Centre for Gene Therapeutics, McMaster University, 1200 Main St. West, Hamilton, Ontario, Canada L8N 3Z5. Phone: (905) 525-9140. Fax: (905) 522-6750. E-mail: mossk{at}mcmaster.ca.

Journal of Virology, February 2004, p. 1675-1684, Vol. 78, No. 4
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.4.1675-1684.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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