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Journal of Virology, December 2009, p. 12108-12117, Vol. 83, No. 23
0022-538X/09/$08.00+0     doi:10.1128/JVI.01575-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Maribavir Inhibits Epstein-Barr Virus Transcription in Addition to Viral DNA Replication {triangledown} ,{dagger}

Fu-Zhang Wang, Debasmita Roy, Edward Gershburg,{ddagger} Christopher B. Whitehurst, Dirk P. Dittmer, and Joseph S. Pagano*

Departments of Microbiology and Immunology and Medicine, Lineberger Comprehensive Cancer Center, Center for AIDS Research, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina

Received 30 July 2009/ Accepted 11 September 2009

Although many drugs inhibit the replication of Epstein-Barr virus (EBV) in cell culture systems, there is still no drug that is effective and approved for use in primary EBV infection. More recently, maribavir (MBV), an L-ribofuranoside benzimidazole, has been shown to be a potent and nontoxic inhibitor of EBV replication and to have a mode of action quite distinct from that of acyclic nucleoside analogs such as acyclovir (ACV) that is based primarily on MBV's ability to block the phosphorylation of target proteins by EBV and human cytomegalovirus protein kinases. However, since the antiviral mechanisms of the drug are complex, we have carried out a comprehensive analysis of the effects of MBV on the RNA expression levels of all EBV genes with a quantitative real-time reverse transcription-PCR-based array. We show that in comparisons with ACV, the RNA expression profiles produced by the two drugs are entirely different, with MBV causing a pronounced inhibition of multiple viral mRNAs and with ACV causing virtually none. The results emphasize the different modes of action of the two drugs and suggest that the action of MBV may be linked to indirect effects on the transcription of EBV genes through the interaction of BGLF4 with multiple viral proteins.

* Corresponding author. Mailing address: Departments of Microbiology and Immunology and Medicine, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7295. Phone: (919) 966-1183. Fax: (919) 966-9673. E-mail: joseph_pagano{at}med.unc.edu

{triangledown} Published ahead of print on 16 September 2009.

{dagger} Supplemental material for this article may be found at http://jvi.asm.org/.

{ddagger} Present address: Department of Medical Microbiology, Immunology and Cell Biology, Southern Illinois University School of Medicine, Springfield, IL 62794.

Journal of Virology, December 2009, p. 12108-12117, Vol. 83, No. 23
0022-538X/09/$08.00+0     doi:10.1128/JVI.01575-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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