NDLI: The antiherpetic drug acyclovir inhibits HIV replication and selects the V75I reverse transcriptase multidrug resistance mutation.

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The antiherpetic drug acyclovir inhibits HIV replication and selects the V75I reverse transcriptase multidrug resistance mutation.

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The antiherpetic drug acyclovir inhibits HIV replication and selects the V75I reverse transcriptase multidrug resistance mutation.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Siliciano, Janet D. Siliciano, Robert F. Stivers, James T. Lai, Jun Kohli, Rahul M. Liu, Jun O. Mcmahon, Moira A.
Description	Author Affiliation: McMahon MA ( Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.)
Abstract	The antiviral drug acyclovir is a guanosine nucleoside analog that potently inhibits herpes simplex virus (HSV) replication. Acyclovir treatment in patients coinfected with HSV and human immunodeficiency virus (HIV) has been observed to alter disease course and decrease HIV viral load, a finding that has been attributed to indirect effects of HSV suppression on HIV replication. Based on this hypothesis, several clinical studies have recently investigated the use of acyclovir for treatment of patients coinfected with HSV and HIV or for prophylaxis against HIV transmission. In this report, we use a single round HIV infectivity assay to show that acyclovir directly inhibits HIV infection with an IC50 of approximately 5 microm. The target of acyclovir in HIV-infected cells is validated as HIV reverse transcriptase (RT) by the emergence of the RT variant V75I under the selective pressure of acyclovir. The V75I mutation is part of the multidrug resistance pathway that enhances viral resistance to many of the best RT inhibitors approved for the treatment of HIV. Biochemical analyses demonstrate that acyclovir triphosphate is a chain terminator substrate for HIV RT and can compete with dGTP for incorporation into DNA. Although acyclovir may prove a useful lead for development of new HIV treatments, the selection of resistant mutants raises a cautionary note to the use of acyclovir monotherapy in patients coinfected with HSV and HIV.
ISSN	00219258
e-ISSN	1083351X
Journal	Journal of Biological Chemistry
Issue Number	46
Volume Number	283
Language	English
Publisher	American Society for Biochemistry and Molecular Biology (United States)
Publisher Date	2008-11-14
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Acyclovir Pharmacology Antiviral Agents Drug Resistance, Multiple, Viral Drug Effects HIV Reverse Transcriptase Antagonists & Inhibitors HIV Enzymology Virus Replication Genetics Metabolism Mutation Simplexvirus Substrate Specificity Valine Research Support, N.I.H., Extramural Biochemistry Molecular Biology
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry Molecular Biology

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