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

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 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.

SUBMITTER: Wei M

PROVIDER: S-EPMC2593337 | biostudies-literature | 2008 Dec

REPOSITORIES: biostudies-literature

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

Wei Min M Yang Yiliang Y Niu Meijuan M Desfosse Laurie L Kennedy Robert R Musier-Forsyth Karin K Kleiman Lawrence L

Journal of virology 20081008 24

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 transcri ...[more]

PMID: 18842718

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Project description:Feline immunodeficiency virus (FIV) Vif protein counteracts feline APOBEC3s (FcaA3s) restriction factors by inducing their proteasomal degradation. The functional domains in FIV Vif for interaction with FcaA3s are poorly understood. Here, we have identified several motifs in FIV Vif that are important for selective degradation of different FcaA3s. Cats (Felis catus) express three types of A3s: single-domain A3Z2, single-domain A3Z3, and double-domain A3Z2Z3. We proposed that FIV Vif would selectively interact with the Z2 and the Z3 A3s. Indeed, we identified two N-terminal Vif motifs (12LF13 and 18GG19) that specifically interacted with the FcaA3Z2 protein but not with A3Z3. In contrast, the exclusive degradation of FcaA3Z3 was regulated by a region of three residues (M24, L25, and I27). Only a FIV Vif carrying a combination of mutations from both interaction sites lost the capacity to degrade and counteract FcaA3Z2Z3. However, alterations in the specific A3s interaction sites did not affect the cellular localization of the FIV Vif protein and binding to feline A3s. Pulldown experiments demonstrated that the A3 binding region localized to FIV Vif residues 50 to 80, outside the specific A3 interaction domain. Finally, we found that the Vif sites specific to individual A3s are conserved in several FIV lineages of domestic cat and nondomestic cats, while being absent in the FIV Vif of pumas. Our data support a complex model of multiple Vif-A3 interactions in which the specific region for selective A3 counteraction is discrete from a general A3 binding domain.Both human immunodeficiency virus (HIV) and feline immunodeficiency virus (FIV) Vif proteins counteract their host's APOBEC3 restriction factors. However, these two Vif proteins have limited sequence homology. The molecular interaction between FIV Vif and feline APOBEC3s are not well understood. Here, we identified N-terminal FIV Vif sites that regulate the selective interaction of Vif with either feline APOBEC3Z2 or APOBEC3Z3. These specific Vif sites are conserved in several FIV lineages of domestic cat and nondomestic cats, while being absent in FIV Vif from puma. Our findings provide important insights for future experiments describing the FIV Vif interaction with feline APOBEC3s and also indicate that the conserved feline APOBEC3s interaction sites of FIV Vif allow FIV transmissions in Felidae.

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

Publications

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

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