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Journal of Virology, October 2000, p. 8938-8945, Vol. 74, No. 19
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Association of Human Immunodeficiency Virus Type 1 Vif with RNA and Its Role in Reverse Transcription

Markus Dettenhofer,1 Shan Cen,2 Bradley A. Carlson,3 Lawrence Kleiman,2,4 and Xiao-Fang Yu1,*

Department of Molecular Microbiology and Immunology, Johns Hopkins University School of Hygiene and Public Health, Baltimore, Maryland 21205,1 Basic Research Laboratory, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892,3 and Lady Davis Institute for Medical Research and McGill AIDS Centre, Jewish General Hospital,2 and Departments of Medicine and Immunology and Microbiology, McGill University,4 Montreal, Quebec, Canada H3T 1E2

Received 9 May 2000/Accepted 11 July 2000

The vif gene of human immunodeficiency virus type 1 (HIV-1) is essential for viral replication, although the functional target of Vif remains elusive. HIV-1 vif mutant virions derived from nonpermissive H9 cells displayed no significant differences in the amount, ratio, or integrity of their protein composition relative to an isogenic wild-type virion. The amounts of the virion-associated viral genomic RNA and tRNA3Lys were additionally present at normal levels in vif mutant virions. We demonstrate that Vif associates with RNA in vitro as well as with viral genomic RNA in virus-infected cells. A functionally conserved lentivirus Vif motif was found in the double-stranded RNA binding domain of Xenopus laevis, Xlrbpa. The natural intravirion reverse transcriptase products were markedly reduced in vif mutant virions. Moreover, purified vif mutant genomic RNA-primer tRNA complexes displayed severe defects in the initiation of reverse transcription with recombinant reverse transcriptase. These data point to a novel role for Vif in the regulation of efficient reverse transcription through modulation of the virion nucleic acid components.

* Corresponding author. Mailing address: Johns Hopkins University School of Hygiene and Public Health, Department of Molecular Microbiology and Immunology, 615 N. Wolfe St., Baltimore, MD 21205. Phone: (410) 955-3768. Fax: (410) 955-0105. E-mail: xfyu{at}jhsph.edu.

Journal of Virology, October 2000, p. 8938-8945, Vol. 74, No. 19
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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