Inhibition of initiation of reverse transcription in HIV-1 by human APOBEC3F

Yang, Yiliang; Guo, Fei; Cen, Shan; Kleiman, Lawrence

doi:10.1016/j.virol.2007.03.022

Cited by 64 publications

(54 citation statements)

References 44 publications

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“…Upon infection of new target cells, the packaged A3G induces C-to-U modifications in the newly reverse-transcribed minus-strand viral DNA, resulting in hypermutation of the viral genome (30,40,48,78,90,94). Virion-packaged A3G has also been reported to suppress viral activity by inhibiting reverse transcription and integration and/or by inducing viral DNA degradation (3,5,28,35,43,50,54,56,69,70,88).…”

mentioning

confidence: 99%

A Single Amino Acid Difference in Human APOBEC3H Variants Determines HIV-1 Vif Sensitivity

Zhen

Wang

Zhao

et al. 2010

J Virol

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Several variants of APOBEC3H (A3H) have been identified in different human populations. Certain variants of this protein are particularly potent inhibitors of retrotransposons and retroviruses, including HIV-1. However, it is not clear whether HIV-1 Vif can recognize and suppress the antiviral activity of A3H variants, as it does with other APOBEC3 proteins. We now report that A3H_Haplotype II (HapII), a potent inhibitor of HIV-1 in the absence of Vif, can indeed be degraded by HIV-1 Vif. Vif-induced degradation of A3H_HapII was blocked by the proteasome inhibitor MG132 and a Cullin5 (Cul5) dominant negative mutant. In addition, Vif mutants that were incapable of assembly with the host E3 ligase complex factors Cul5, ElonginB, and ElonginC were also defective for A3H_HapII suppression. Although we found that Vif hijacks the same E3 ligase to degrade A3H_HapII as it does to inactivate APOBEC3G (A3G) and APOBEC3F (A3F), more Vif motifs were involved in A3H_HapII inactivation than in either A3G or A3F suppression. In contrast to A3H_HapII, A3H_Haplotype I (HapI), which differs in only three amino acids from A3H_HapII, was resistant to HIV-1 Vif-mediated degradation. We also found that residue 121 was critical for determining A3H sensitivity and binding to HIV-1 Vif.The apolipoprotein B mRNA-editing catalytic polypeptide 3 (APOBEC3) protein family is composed of cytidine deaminases that are capable of editing nucleic acids, converting cytidines to uracils (2,12,15,18,26,27,31,45,82,91). Members of this family of host cell proteins (APOBEC3A, -B, -C, -DE, -F, -G, and -H) have been shown to have differential inhibitory effects on various retroviruses and retroelements that are mediated through cytidine deamination and other mechanisms (4,

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confidence: 99%

A Single Amino Acid Difference in Human APOBEC3H Variants Determines HIV-1 Vif Sensitivity

Zhen

Wang

Zhao

et al. 2010

J Virol

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“…In the absence of HIV-1 accessory protein viral infectivity factor (Vif), A3G will be encapsidated into HIV-1 virions and cause G-to-A hypermutations in the newly synthesized viral DNA (28,36,46,47,78). A3G exerts inhibitory effects at several steps of HIV-1 replication, such as reverse transcription and viral DNA integration (3,8,25,26,30,32,38,44,46,47,49,50,75). Soon after the identification of the antiviral function of A3G, other APOBEC family members, namely, APOBEC3F (A3F), APOBEC3DE, and APOBEC3H, were also proposed as host restriction factors of HIV-1 (7,18,20,27,37,40,56,66,70,79).…”

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confidence: 99%

N-Terminal Hemagglutinin Tag Renders Lysine-Deficient APOBEC3G Resistant to HIV-1 Vif-Induced Degradation by Reduced Polyubiquitination

Wang

Shao

et al. 2011

J Virol

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APOBEC3G, a potent HIV-1 host restriction factor, is overcome by HIV-1 viral infectivity factor (Vif), which induces its polyubiquitination and proteasomal degradation. Here we show that lysine-deficient APOBEC3G with an N-terminal hemagglutinin (HA) tag fusion (HA-A3G20K/R) was resistant to HIV-1 Vif-induced proteasomal degradation. HA-A3G20K/R molecules were packaged into wild-type HIV-1 particles, and HA-A3G20K/R drastically decreased wild-type HIV-1 reverse transcription products and infectivity. We also showed that the N terminus of A3G was a target of polyubiquitination induced by HIV-1 Vif. Thus, fusion of the HA tag to the N terminus of A3G20K/R reduced its polyubiquitination, the likely mechanism for the resistance of this protein to HIV-1 Vif-induced proteasomal degradation. Finding such ways to induce resistance of A3G to Vif may provide new approaches to anti-HIV/AIDS therapy.

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“…Recently, Kleiman and coworkers performed a thorough analysis of reverse transcription defects in ⌬vif virions produced from permissive cells transiently expressing hA3G or hA3F (79,253). In these virions, the priming of reverse transcription, i.e., the addition of the first 6 nucleotides to the primer tRNA 3 Lys , was reduced to ϳ50% of WT levels, which coincided with a strong diminution of minus-strand strong-stop and late DNA products (Table 3).…”

Section: Deamination-independent Activity Of Ha3f and Ha3gmentioning

confidence: 99%

“…Gag is (one of) the main deaminase-independent antiviral mechanism(s) of hA3G and hA3F (80,134,253). This antiviral mechanism might be compensated for by Vif-mediated tRNA 3 Lys annealing (90).…”

Section: Vif Prevents Incorporation Of Ha3g In Hiv-1 Particlesmentioning

confidence: 99%

Tumultuous Relationship between the Human Immunodeficiency Virus Type 1 Viral Infectivity Factor (Vif) and the Human APOBEC-3G and APOBEC-3F Restriction Factors

Henriet

Mercenne

Bernacchi

et al. 2009

Microbiol Mol Biol Rev

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SUMMARY The viral infectivity factor (Vif) is dispensable for human immunodeficiency virus type 1 (HIV-1) replication in so-called permissive cells but is required for replication in nonpermissive cell lines and for pathogenesis. Virions produced in the absence of Vif have an aberrant morphology and an unstable core and are unable to complete reverse transcription. Recent studies demonstrated that human APOBEC-3G (hA3G) and APOBEC-3F (hA3F), which are selectively expressed in nonpermissive cells, possess strong anti-HIV-1 activity and are sufficient to confer a nonpermissive phenotype. Vif induces the degradation of hA3G and hA3F, suggesting that its main function is to counteract these cellular factors. Most studies focused on the hypermutation induced by the cytidine deaminase activity of hA3G and hA3F and on their Vif-induced degradation by the proteasome. However, recent studies suggested that several mechanisms are involved both in the antiviral activity of hA3G and hA3F and in the way Vif counteracts these antiviral factors. Attempts to reconcile the studies involving Vif in virus assembly and stability with these recent findings suggest that hA3G and hA3F partially exert their antiviral activity independently of their catalytic activity by destabilizing the viral core and the reverse transcription complex, possibly by interfering with the assembly and/or maturation of the viral particles. Vif could then counteract hA3G and hA3F by excluding them from the viral assembly intermediates through competition for the viral genomic RNA, by regulating the proteolytic processing of Pr55Gag, by enhancing the efficiency of the reverse transcription process, and by inhibiting the enzymatic activities of hA3G and hA3F.

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Inhibition of initiation of reverse transcription in HIV-1 by human APOBEC3F

Cited by 64 publications

References 44 publications

A Single Amino Acid Difference in Human APOBEC3H Variants Determines HIV-1 Vif Sensitivity

A Single Amino Acid Difference in Human APOBEC3H Variants Determines HIV-1 Vif Sensitivity

N-Terminal Hemagglutinin Tag Renders Lysine-Deficient APOBEC3G Resistant to HIV-1 Vif-Induced Degradation by Reduced Polyubiquitination

Tumultuous Relationship between the Human Immunodeficiency Virus Type 1 Viral Infectivity Factor (Vif) and the Human APOBEC-3G and APOBEC-3F Restriction Factors

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