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Journal of Virology, December 2008, p. 12049-12059, Vol. 82, No. 24
0022-538X/08/$08.00+0     doi:10.1128/JVI.01744-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Inability of Human Immunodeficiency Virus Type 1 Produced in Murine Cells To Selectively Incorporate Primer Formula{triangledown} ,{dagger}

Min Wei,1 Yiliang Yang,1 Meijuan Niu,1 Laurie Desfosse,1 Robert Kennedy,4 Karin Musier-Forsyth,5 and Lawrence Kleiman1,2,3*

Lady Davis Institute for Medical Research and McGill AIDS Centre, Jewish General Hospital, Montreal, Quebec H3T 1E2, Canada,1 Department of Medicine,2 Department of Microbiology and Immunology, McGill University, Montreal, Quebec H3T 1E2, Canada,3 Department of Chemistry, University of Minnesota, Minneapolis, Minnesota, 55455,4 Departments of Chemistry and Biochemistry, The Ohio State University, Columbus, Ohio 432105

Received 18 August 2008/ Accepted 2 October 2008

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

* Corresponding author. Mailing address: Lady Davis Institute for Medical Research, Jewish General Hospital, 3755 Cote St. Catherine Rd., Montreal, Quebec, Canada H3T 1E2. Phone: (514) 340-8260. Fax: (514) 340-7502. E-mail: lawrence.kleiman{at}mcgill.ca

{triangledown} Published ahead of print on 8 October 2008.

{dagger} Supplemental material for this article may be found at http://jvi.asm.org/.

Journal of Virology, December 2008, p. 12049-12059, Vol. 82, No. 24
0022-538X/08/$08.00+0     doi:10.1128/JVI.01744-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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