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In vitro fidelity of the prototype primate foamy virus (PFV) RT compared to HIV-1 RT.

ABSTRACT: We compared the in vitro fidelity of wild-type human immunodeficiency virus type-1 (HIV-1) reverse transcriptase (RT) and the prototype foamy virus (PFV) RT. Both enzymes had similar error rates for single nucleotide substitutions; however, PFV RT did not appear to make errors at specific hotspots, like HIV-1 RT. In addition, PFV RT made more deletions and insertions than HIV-1 RT. Although the majority of the missense errors made by HIV-1 RT and PFV RT are different, relatively few of the mutations caused by either enzyme can be explained by a misalignment/slippage mechanism. We suggest that the higher polymerase activity of PFV RT could contribute to the ability of the enzyme to jump to the same or a different template.

SUBMITTER: Boyer PL

PROVIDER: S-EPMC2720797 | biostudies-literature | 2007 Oct

REPOSITORIES: biostudies-literature

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In vitro fidelity of the prototype primate foamy virus (PFV) RT compared to HIV-1 RT.

Boyer Paul L PL Stenbak Carolyn R CR Hoberman David D Linial Maxine L ML Hughes Stephen H SH

Virology 20070712 2

We compared the in vitro fidelity of wild-type human immunodeficiency virus type-1 (HIV-1) reverse transcriptase (RT) and the prototype foamy virus (PFV) RT. Both enzymes had similar error rates for single nucleotide substitutions; however, PFV RT did not appear to make errors at specific hotspots, like HIV-1 RT. In addition, PFV RT made more deletions and insertions than HIV-1 RT. Although the majority of the missense errors made by HIV-1 RT and PFV RT are different, relatively few of the mutat ...[more]

PMID: 17631930

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Project description:Foamy viruses (FVs) are complex retroviruses belonging to the Spumaretrovirinae subfamily of the Retroviridae family. In contrast to human immunodeficiency virus (HIV), another member of the Retroviridae family, FVs are nonpathogenic in their natural hosts or in experimentally infected animals. Prototype foamy virus (PFV) is the only foamy virus that can infect humans through cross-species transmission and does not show any pathogenicity after infection. Consequently, PFV is considered a safe and efficient gene transfer vector. Understanding the host proteins involved in the replication of PFV and the mechanism of interaction between the host and the virus might lead to studies to improve the efficiency of gene transfer. To date, only a few host factors have been identified that affect PFV replication. In the present study, we report that PFV infection enhances the promoter activity of SGK1 (encoding serum/glucocorticoid regulated kinase 1) via the Tas protein signaling pathway, and then upregulates the mRNA and protein levels of SGK1. Overexpression of SGK1 reduced PFV replication, whereas its depletion using small interfering RNA increased PFV replication. SGK1 inhibits PFV replication by impairing the function of the PFV Tas activation domain in a kinase-independent manner and reducing the stability of the Gag protein in a kinase-dependent manner. In addition, both human and bovine SGK1 proteins inhibit the replication of bovine foamy virus (BFV) and PFV. These findings not only improved our understanding of the function of SGK1 and its relationship with foamy viruses, but also contributed to determining the antiviral mechanism of the host. IMPORTANCE Foamy viruses can integrate into the host chromosome and are nonpathogenic in natural hosts or in experimentally infected animals. Therefore, foamy viruses are considered to be safe and efficient gene transfer vectors. Persistent infection of foamy viruses is partly caused by the restrictive effect of host factors on the virus. However, only a few cellular proteins are known to influence the replication of foamy viruses. In this study, we report that SGK1 inhibits the replication of prototype foamy virus by affecting the function of the transcription activator, Tas, and reducing the stability of the structural protein, Gag. These results will increase our understanding of the interaction between the virus and host factors, deepening our perception of host antiviral defenses and the function of SGK1, and could improve the gene transfer efficiency of foamy viruses.

Dataset Information

In vitro fidelity of the prototype primate foamy virus (PFV) RT compared to HIV-1 RT.

Publications

In vitro fidelity of the prototype primate foamy virus (PFV) RT compared to HIV-1 RT.

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