Association of Human Immunodeficiency Virus Type 1 Vif with RNA and Its Role in Reverse Transcription

Dettenhofer, Markus; Cen, Shan; Carlson, Bradley A.; Kleiman, Lawrence; Yu, Xiaofang

doi:10.1128/jvi.74.19.8938-8945.2000

Cited by 100 publications

(118 citation statements)

References 44 publications

(29 reference statements)

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“…It is possible that the interaction of APOBEC3G with nucleocapsid might result in the inhibition of viral functions associated with nucleocapsid. For example, Gag nucleocapsid sequences facilitate tRNA annealing to viral genomic RNA (53), which could explain the observation that deproteinized viral RNA (which contains primer tRNA annealed to viral genomic RNA) extracted from Vif-negative HIV-1 produced in non-permissive cells shows a decreased ability to support reverse transcription in vitro compared with the same RNA extracted from similar virions produced in permissive cells (8). Alternatively, this observation might reflect the presence in non-permissive cells of other anti-HIV-1 factors yet to be discovered.…”

Section: Discussionmentioning

confidence: 99%

The Interaction between HIV-1 Gag and APOBEC3G

Cen

Guo

Niu

et al. 2004

Journal of Biological Chemistry

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APOBEC3G, a member of an RNA/DNA cytidine deaminase superfamily, has been identified as a cellular inhibitor of HIV-1 infectivity, possibly through the dC to dU deamination of the first minus strand cDNA synthesized during reverse transcription. Virions incorporate APOBEC3G during viral assembly in non-permissive cells, and this incorporation is inhibited by the viral protein Vif. The mechanism of APOBEC3G incorporation into HIV-1 is examined in this report. In the absence of Vif, cytoplasmic APOBEC3G becomes membranebound in cells expressing HIV-1 Gag, and its incorporation into Gag viral-like particles (VLPs) is proportional to the amount of APOBEC3G expressed in the cell. The expression of Vif, or mutant Gag unable to bind to membrane, prevents the APOBEC3G association with membrane. HIV-1 Gag alone among viral proteins is sufficient for packaging of APOBEC3G into Gag VLPs, and this incorporation requires the presence of Gag nucleocapsid. The presence of amino acids 104 -156 in APOBEC3G, located in the linker region between two zinc coordination motifs, is also required for its incorporation into Gag VLPs. Evidence against an RNA bridge facilitating the Gag/APOBEC3G interaction includes data indicating that 1) the incorporation of APOBEC3G occurs independently of viral genomic RNA, 2) a Gag/APOBEC3G complex is immunoprecipitated from cell lysate after RNase treatment, and 3) the zinc coordination motif, rather than the regions flanking this motif, have been implicated in RNA binding in another family member, APOBEC1.

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Section: Discussionmentioning

confidence: 99%

The Interaction between HIV-1 Gag and APOBEC3G

Cen

Guo

Niu

et al. 2004

Journal of Biological Chemistry

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234

237

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“…Studies have suggested that either reverse transcription fails to proceed to completion or that reverse transcripts are unstable, possibly depending on the identity of the target cell (14,15,18,46,60,67). Correspondingly, several groups have found ⌬vif virions to be par-tially defective in endogenous reverse transcriptase (RT) assays (17,18,27,46,48). Whether these findings are indicative of a specific problem with the reverse transcription complex, structural abnormalities in the viral core (6,9,32,48), or some other molecular defect in virions is unknown.…”

mentioning

confidence: 99%

“…To date, no reproducible quantitative or qualitative difference in the protein content of wild-type and ⌬vif virions has been reported, aside from a difference in Vif incorporation (6,11,22,38,39,42,61) and a controversial difference in Gag processing (6,56). Recent work has suggested, however, that primer tRNA 3 Lysgenomic RNA complexes from ⌬vif virions may be unable to prime efficient reverse transcription (17).…”

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confidence: 99%

Comprehensive Investigation of the Molecular Defect in vif -Deficient Human Immunodeficiency Virus Type 1 Virions

Gaddis

Chertova

Sheehy

et al. 2003

J Virol

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Replication of human immunodeficiency virus type 1 (HIV-1) in primary blood lymphocytes, certain T-cell lines (nonpermissive cells), and most likely in vivo is highly dependent on the virally encoded Vif protein.Evidence suggests that Vif acts late in the viral life cycle during assembly, budding, and/or maturation to counteract the antiviral activity of the CEM15 protein and possibly other antiviral factors. Because HIV-1 virions produced in the absence of Vif are severely restricted at a postentry, preintegration step of infection, it is presumed that such virions differ from wild-type virions in some way. In the present study, we established a protocol for producing large quantities of vif-deficient HIV-1 (HIV-1/⌬vif) from an acute infection of nonpermissive T cells and performed a thorough examination of the defect in these virions. Aside from the expected lack of Vif, we observed no apparent abnormalities in the packaging, modification, processing, or function of proteins in ⌬vif virions. In addition, we found no consistent defect in the ability of ⌬vif virions to perform intravirion reverse transcription under a variety of assay conditions, suggesting that the reverse transcription complexes in these particles can behave normally under cell-free conditions. Consistent with this finding, neither the placement of the primer tRNA 3 Lys nor its ability to promote reverse transcription in an in vitro assay was affected by a lack of Vif. Based on the inability of this comprehensive analysis to uncover molecular defects in ⌬vif virions, we speculate that such defects are likely to be subtle and/or rare.

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“…However, recent studies indicate that Vif is required to counteract the endogenous inhibitor CEM15, which is a putative cytidine deaminase (19,35). Because Vif binds to HIV-1 RNA, it is reasonable to assume that Vif-RNA binding could protect the HIV-RNA from RNA editing (20,21). If so, Vif-RNA binding could be the major mechanism for Vif function.…”

Section: Identification Of Pxp Motif-containing Peptides Binding Tomentioning

confidence: 99%

“…Because its sequence is similar with APOBEC-1(apoB mRNA-editing catalytic subunit 1), a cytidine deaminase that can change cytidine into uridine in the mRNA of apolipoprotein B, CEM15 could affect the genomic RNA of HIV-1. Interestingly, we and others show that Vif is an RNA-binding protein and is an integral component of a messenger ribonucleotide protein complex of viral RNA (20,21). The Vif protein in this ribonucleoprotein complex may protect viral RNA from various endogenous inhibitors and could mediate viral RNA engagement with HIV-1 Gag precursors.…”

mentioning

confidence: 99%