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Journal of Virology, February 2005, p. 1975-1980, Vol. 79, No. 3
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.3.1975-1980.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

G->A Hypermutation in Protease and Reverse Transcriptase Regions of Human Immunodeficiency Virus Type 1 Residing in Resting CD4+ T Cells In Vivo

Tara L. Kieffer,1 Patty Kwon,1 Richard E. Nettles,1 Yefei Han,1 Stuart C. Ray,1 and Robert F. Siliciano1,2*

Department of Medicine, Johns Hopkins University School of Medicine,1 Howard Hughes Medical Institute, Baltimore, Maryland2

Received 10 August 2004/ Accepted 9 September 2004

In vitro studies have shown that the host cytidine deaminase APOBEC3G causes lethal hypermutation in human immunodeficiency virus type 1 reverse transcripts unless its incorporation into virions is blocked by Vif. By examining stably archived sequences in resting CD4+ T cells, we show that hypermutation occurs in most if not all infected individuals. Hypermutated sequences comprised >9% of archived species in resting CD4+ T cells but were not found in plasma virus. Mutations occurred in predicted contexts, with notable hotspots. Thus, defects in Vif function in vivo give rise to hypermutated viral genomes that can be integrated but do not produce progeny viruses.

* Corresponding author. Mailing address: Department of Medicine, Johns Hopkins University School of Medicine, 879 Broadway Research Bldg., 733 N. Broadway, Baltimore, MD 21205. Phone: (410) 955-2958. Fax: (443) 287-6218. E-mail: rsiliciano{at}jhmi.edu.

Journal of Virology, February 2005, p. 1975-1980, Vol. 79, No. 3
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.3.1975-1980.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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