Inability of human immunodeficiency virus type 1 produced in murine cells to selectively incorporate primer formula.

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 tRNA(3Lys) into HIV-1 produced in murine cells. HIV-1 and murine leukemia virus (MuLV) use tRNA(3Lys) and tRNA(Pro), respectively, as primers for reverse transcription. Selective packaging of tRNA(3Lys) 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 tRNA(3Lys) 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 tRNA(3Lys) to an MuLV-like packaging of tRNA(Pro). The primer binding site in viral RNA remains complementary to tRNA(3Lys), resulting in a significant decrease in reverse transcription and infectivity. Reduction in tRNA(3Lys) 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 tRNA(3Lys) into another retrovirus that uses tRNA(3Lys) as a primer, the mouse mammary tumor virus.