Affiliation:
1. Lady Davis Institute for Medical Research and McGill AIDS Centre, Jewish General Hospital, Montreal, Quebec H3T 1E2, Canada
2. Department of Chemistry, University of Minnesota, Minneapolis, Minnesota, 55455
3. Departments of Chemistry and Biochemistry, The Ohio State University, Columbus, Ohio 43210
4. Department of Medicine
5. Department of Microbiology and Immunology, McGill University, Montreal, Quebec H3T 1E2, Canada
Abstract
ABSTRACT
Attempts to use the mouse as a model system for studying AIDS are stymied by the multiple blocks to human immunodeficiency virus type 1 (HIV-1) replication that exist in mouse cells at the levels of viral entry, transcription, and Gag assembly and processing. In this report, we describe an additional block in the selective packaging of
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into HIV-1 produced in murine cells. HIV-1 and murine leukemia virus (MuLV) use
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and tRNA
Pro
, respectively, as primers for reverse transcription. Selective packaging of
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into HIV-1 produced in human cells is much stronger than that for tRNA
Pro
incorporation into MuLV produced in murine cells, and different packaging mechanisms are used. Thus, both lysyl-tRNA synthetase and GagPol are required for
\batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(tRNA_{3}^{Lys}\) \end{document}
packaging into HIV-1, but neither prolyl-tRNA synthetase nor GagPol is required for tRNA
Pro
packaging into MuLV. In this report, we show that when HIV-1 is produced in murine cells, the virus switches from an HIV-1-like incorporation of
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to an MuLV-like packaging of tRNA
Pro
. The primer binding site in viral RNA remains complementary to
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, resulting in a significant decrease in reverse transcription and infectivity. Reduction in
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incorporation occurs even though both murine lysyl-tRNA synthetase and HIV-1 GagPol are packaged into the HIV-1 produced in murine cells. Nevertheless, the murine cell is able to support the select incorporation of
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into another retrovirus that uses
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as a primer, the mouse mammary tumor virus.
Publisher
American Society for Microbiology
Subject
Virology,Insect Science,Immunology,Microbiology
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