APOBEC3G Is Incorporated into Virus-like Particles by a Direct Interaction with HIV-1 Gag Nucleocapsid Protein

Alce, Timothy M.; Popik, Waldemar

doi:10.1074/jbc.c400235200

Cited by 220 publications

(203 citation statements)

References 34 publications

(25 reference statements)

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“…It is relevant that the C terminus of HTLV-1 NC contributes to the exclusion of hA3G from VLPs, because it is NC that brings viral and cellular RNAs into the virion. It is currently believed that both NC and RNA are necessary for incorporation of hA3G into virions (19,20,22,(32)(33)(34), but it is unclear whether hA3G is simply tethered to RNA (21,22,34) or interacts with a NC-RNA complex (11). Deleting 20 aa near the C terminus of HTLV-1 NC (NCDC mutant) did not alter the amount of viral RNA in virions but did increase the amount of hA3G that was packaged.…”

Section: Discussionmentioning

confidence: 99%

“…Although cytosine deaminase activity appears to correlate with antiviral activity of hA3G, there is evidence that other factors may contribute to antiviral activity, and it is still unclear which stage of the virus infectious cycle is primarily affected (16)(17)(18). The exact mechanism by which hA3G is packaged into virions is also unresolved but it does appear to require both RNA and viral nucleocapsid (NC) protein (19)(20)(21)(22). HIV-1 counteracts the effects of hA3G with the accessory protein Vif, whose primary function is to target hA3G for proteasomal degradation, thereby preventing encapsidation of hA3G into virus particles (23)(24)(25)(26)(27)(28).…”

Section: Ells Have Evolved Numerous Strategies To Restrict Infectionmentioning

confidence: 99%

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Resistance of human T cell leukemia virus type 1 to APOBEC3G restriction is mediated by elements in nucleocapsid

Derse

Hill

Princler

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

113

118

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Human T cell leukemia virus type 1 (HTLV-1) has evolved a remarkable strategy to thwart the antiviral effects of the cellular cytidine deaminase APOBEC3G (hA3G). HTLV-1 infects T lymphocytes in vivo, where, like HIV-1, it is likely to encounter hA3G. HIV-1 counteracts the innate antiviral activity of hA3G by producing an accessory protein, Vif, which hastens the degradation of hA3G. In contrast, HTLV-1 does not encode a Vif homologue; instead, HTLV-1 has evolved a cis-acting mechanism to prevent hA3G restriction. We demonstrate here that a peptide motif in the C terminus of the HTLV-1 nucleocapsid (NC) domain inhibits hA3G packaging into nascent virions. Mutation of amino acids within this region resulted in increased levels of hA3G incorporation into virions and increased susceptibility to hA3G restriction. Elements within the C-terminal extension of the NC domain are highly conserved among the primate T cell leukemia viruses, but this extension is absent in all other retroviral NC proteins.

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Section: Discussionmentioning

confidence: 99%

Section: Ells Have Evolved Numerous Strategies To Restrict Infectionmentioning

confidence: 99%

Resistance of human T cell leukemia virus type 1 to APOBEC3G restriction is mediated by elements in nucleocapsid

Derse

Hill

Princler

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

113

118

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“…In a retrovirus-infected cell, this localization may facilitate the incorporation of APOBEC3G into viral particles, which are released from the plasma membrane. APOBEC3G is also specifically incorporated into virions through an association with the viral Gag protein and͞or viral genomic RNA (12)(13)(14)(15)(16)(17)(18). Once a retrovirus enters a cell, its genomic RNA is reverse transcribed, and during this process, APOBEC3G is capable of deaminating cDNA cytosines to uracils (C 3 U).…”

mentioning

confidence: 99%

APOBEC3G hypermutates genomic DNA and inhibits Ty1 retrotransposition in yeast

Schumacher

Nissley

Harris

2005

Proc. Natl. Acad. Sci. U.S.A.

137

111

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Human cells harbor a variety of factors that function to block the proliferation of foreign nucleic acid. The APOBEC3G enzyme inhibits the replication of retroviruses by deaminating nascent retroviral cDNA cytosines to uracils, lesions that can result in lethal levels of hypermutation. Here, we demonstrate that APOBEC3G is capable of deaminating genomic cytosines in Saccharomyces cerevisiae. APOBEC3G expression caused a 20-fold increase in frequency of mutation to canavanine-resistance, which was further elevated in a uracil DNA glycosylase-deficient background. All APOBEC3G-induced base substitution mutations mapped to the nuclear CAN1 gene and were exclusively C͞G 3 T͞A transition mutations within a 5 -CC consensus. The APOBEC3G preferred sites were found on both strands of the DNA duplex, but were otherwise located in hotspots nearly identical to those found previously in retroviral cDNA. This unique genetic system further enabled us to show that expression of APOBEC3G or its homolog APOBEC3F was able to inhibit the mobility of the retrotransposon Ty1 by a mechanism that involves the deamination of cDNA cytosines. Thus, these data expand the range of likely APOBEC3 targets to include nuclear DNA and endogenous retroelements, which have pathological and physiological implications, respectively. We postulate that the APOBEC3-dependent innate cellular defense constitutes a tightly regulated arm of a conserved mobile nucleic acid restriction mechanism that is poised to limit internal as well as external assaults.APOBEC3F ͉ endogenous retrotransposon Ty1 ͉ hypermutation ͉ cytodeamination ͉ Saccharomyces cerevisiae

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“…As a result, it creates stop codons or G-A transitions in the newly synthesized viral cDNA which is then subjective to elimination by host DNA repair machinery [74,76]. APOBEC3G confers its antiviral effect by encapsidating into the virus particles through interaction with viral Gag protein [77][78][79][80][81]. Thus, APOBEC3G represents an innate host defense mechanism against HIV infection.…”

Section: Virus Infectivity Factor (Vif)mentioning

confidence: 99%

Roles of HIV-1 auxiliary proteins in viral pathogenesis and host-pathogen interactions

Pauza

et al. 2005

Cell Res

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Active host-pathogen interactions take place during infection of human immunodeficiency virus type 1 (HIV-1). Outcomes of these interactions determine the efficiency of viral infection and subsequent disease progression. HIVinfected cells respond to viral invasion with various defensive strategies such as innate, cellular and humoral immune antiviral mechanisms. On the other hand, the virus has also developed various offensive tactics to suppress these host cellular responses. Among many of the viral offensive strategies, HIV-1 viral auxiliary proteins (Tat, Rev, Nef, Vif, Vpr and Vpu) play important roles in the host-pathogen interaction and thus have significant impacts on the outcome of HIV infection. One of the best examples is the interaction of Vif with a host cytidine deaminase APOBEC3G. Although specific roles of other auxiliary proteins are not as well described as Vif-APOBEC3G interaction, it is the goal of this brief review to summarize some of the preliminary findings with the hope to stimulate further discussion and investigation in this exhilarating area of research.

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APOBEC3G Is Incorporated into Virus-like Particles by a Direct Interaction with HIV-1 Gag Nucleocapsid Protein

Cited by 220 publications

References 34 publications

Resistance of human T cell leukemia virus type 1 to APOBEC3G restriction is mediated by elements in nucleocapsid

Resistance of human T cell leukemia virus type 1 to APOBEC3G restriction is mediated by elements in nucleocapsid

APOBEC3G hypermutates genomic DNA and inhibits Ty1 retrotransposition in yeast

Roles of HIV-1 auxiliary proteins in viral pathogenesis and host-pathogen interactions

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