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Journal of Virology, June 2002, p. 5803-5806, Vol. 76, No. 11
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.11.5803-5806.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

A Nucleotide Substitution in the tRNA^Lys Primer Binding Site Dramatically Increases Replication of Recombinant Simian Immunodeficiency Virus Containing a Human Immunodeficiency Virus Type 1 Reverse Transcriptase

Department of Epidemiology and Public Health,¹ Section of Immunobiology, Yale University School of Medicine, New Haven, Connecticut,³ Department of Microbiology, Boston University School of Medicine, Boston,² New England Regional Primate Research Center, Harvard Medical School, Cambridge, Massachusetts⁴

Received 29 November 2001/ Accepted 19 February 2002

A recombinant simian immunodeficiency virus (SIV) derived from strain 239 (SIVmac239) with reverse transcriptase (RT) sequences from human immunodeficiency virus type 1 (HIV-1) strain HXB2 was severely impaired for replication. Detectable p27^Gag levels were not observed until day 65 and peak p27^Gag levels were not reached until day 75 after transfection of CEMx174 cells with the recombinant DNA. Sequences from the latter time point did not contain amino acid substitutions in HIV-1 RT; however, a single nucleotide substitution (thymine to cytosine) was found at position eight of the SIV primer binding site. We engineered an RT/SHIV genome with the thymine-to-cytosine substitution, called RT/SHIV/TC, and observed dramatically faster replication kinetics than were observed with the parental RT/SHIV from which this variant was derived. RT/SHIV/TC provides an improved system for study of the impact of drug resistance mutations in HIV-1 RT in a relevant animal model.

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