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Journal of Virology, March 2005, p. 3217-3222, Vol. 79, No. 5
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.5.3217-3222.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Kaposi's Sarcoma-Associated Herpesvirus/Human Herpesvirus 8 RTA Reactivates Murine Gammaherpesvirus 68 from Latency

Tammy M. Rickabaugh,1 Helen J. Brown,2 Ting-Ting Wu,2 Moon Jung Song,2 Seungmin Hwang,2 Hongyu Deng,2 Katherine Mitsouras,3 and Ren Sun1,2,4,5*

Molecular Biology Institute,1 Department of Molecular and Medical Pharmacology,2 UCLA AIDS Institute and Dental Research Institute,4 Jonsson Comprehensive Cancer Center,5 Department of Biological Chemistry, University of California at Los Angeles, Los Angeles, California3

Received 9 April 2004/ Accepted 7 September 2004

Murine gammaherpesvirus 68 (MHV-68), Kaposi's sarcoma-associated herpesvirus (HHV-8), and Epstein-Barr virus (EBV) are all members of the gammaherpesvirus family, characterized by their ability to establish latency in lymphocytes. The RTA protein, conserved in all gammaherpesviruses, is known to play a critical role in reactivation from latency. Here we report that HHV-8 RTA, not EBV RTA, was able to induce MHV-68 lytic viral proteins and DNA replication and processing and produce viable MHV-68 virions from latently infected cells at levels similar to those for MHV-68 RTA. HHV-8 RTA was also able to activate two MHV-68 lytic promoters, whereas EBV RTA was not. In order to define the domains of RTA responsible for their functional differences in viral promoter activation and initiation of the MHV-68 lytic cycle, chimeric RTA proteins were constructed by exchanging the N-terminal and C-terminal domains of the RTA proteins. Our data suggest that the species specificity of MHV-68 RTA resides in the N-terminal DNA binding domain.

* Corresponding author. Mailing address: Department of Molecular and Medical Pharmacology, University of California at Los Angeles, Los Angeles, CA 90095-1735. Phone: (310) 794-5557. Fax: (310) 825-6267. E-mail: rsun{at}mednet.ucla.edu.

Journal of Virology, March 2005, p. 3217-3222, Vol. 79, No. 5
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.5.3217-3222.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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