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 tRNAPro, 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 tRNAPro incorporation into MuLV produced in murine cells, and different packaging mechanisms are used. Thus, both lysyl-tRNA synthetase and GagPol are required for
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packaging into HIV-1, but neither prolyl-tRNA synthetase nor GagPol is required for tRNAPro 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 tRNAPro. 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.
Selection for Loss of Ref1 Activity in Human Cells Releases Human Immunodeficiency Virus Type 1 from Cyclophilin A Dependence during Infection