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Journal of Virology, February 2005, p. 2420-2431, Vol. 79, No. 4
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.4.2420-2431.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Modulation of Human Herpesvirus 8/Kaposi's Sarcoma-Associated Herpesvirus Replication and Transcription Activator Transactivation by Interferon Regulatory Factor 7

Jinzhong Wang,1,2 Jun Zhang,1 Luwen Zhang,1 William Harrington Jr.,3 John T. West,1 and Charles Wood1*

Nebraska Center for Virology and School of Biological Sciences, University of Nebraska—Lincoln, Lincoln, Nebraska,1 College of Life Sciences, Nankai University, Tianjin, People's Republic of China,2 University of Miami School of Medicine, Miami, Florida3

Received 15 July 2004/ Accepted 5 October 2004

Human herpesvirus 8 (HHV-8)/Kaposi's sarcoma-associated herpesvirus infection goes through lytic and latent phases that are regulated by viral gene products, but very little is known about the involvement of host proteins. The replication and transcription activator (RTA) is a viral protein sufficient to initiate lytic replication by activating downstream genes, including the viral early gene open reading frame 57 (ORF 57), which codes for a posttranscriptional activator. In this study, we demonstrate that cellular interferon regulatory factor 7 (IRF-7) negatively regulates this process by competing with RTA for binding to the RTA response element in the ORF 57 promoter to down-regulate RTA-induced gene expression. We also show that alpha interferon represses RTA-mediated transactivation and that repression involves IRF-7. Our study indicates that upon HHV-8 infection, the host responds by suppression of lytic gene expression through binding of IRF-7 to the lytic viral gene promoter. These findings suggest that HHV-8 has developed a novel mechanism to induce but then subvert the innate antiviral response, specifically the interferon-signaling pathway, to regulate RTA activity and ultimately the viral latent/lytic replicative cycle.

* Corresponding author. Mailing address: Nebraska Center for Virology and School of Biological Sciences, University of Nebraska-Lincoln, E249 Beadle Center, 1901 Vine St., Lincoln, NE 68588-0666. Phone: (402) 472-4550. Fax: (402) 472-8722. E-mail: cwood1{at}unl.edu.

Journal of Virology, February 2005, p. 2420-2431, Vol. 79, No. 4
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.4.2420-2431.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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