APOBEC3G is a single-stranded DNA cytidine deaminase and functions independently of HIV reverse transcriptase

Suspène, Rodolphe; Sommer, Peter; Mathieu, H.; Ferris, Stéphane; Guétard, Denise; Pochet, Sylvie; Chester, Ann; Navaratnam, Naveenan; Wain‐Hobson, Simon; Vartanian, Jean‐Pierre

doi:10.1093/nar/gkh554

Cited by 194 publications

(192 citation statements)

References 58 publications

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“…Encapsidated APOBEC3B and APOBEC3C Deaminate the Reverse Transcripts-APOBEC3G and APOBEC3F mediate their antiviral activity by single-strand DNA deamination (9,10,27,28,34). To determine whether APOBEC3B and APOBEC3C also act through this mechanism, the sequence of viral reverse transcripts from newly infected cells was analyzed.…”

Section: Hiv-1 and Siv Encapsidate Apobec3b And Apobec3c-mentioning

confidence: 99%

APOBEC3B and APOBEC3C Are Potent Inhibitors of Simian Immunodeficiency Virus Replication

Chen

König

et al. 2004

Journal of Biological Chemistry

274

276

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In the human genome the apolipoprotein B mRNAediting enzyme catalytic polypeptide (APOBEC)3 gene has expanded into a tandem array of genes termed APOBEC3A-G. Two members of this family, APOBEC3G and APOBEC3F, have been found to have potent activity against virion infectivity factor deficient (⌬vif) human immunodeficiency virus 1 (HIV-1). These enzymes become encapsidated in ⌬vif HIV-1 virions and in the next round of infection deaminate the newly synthesized reverse transcripts. The lentiviral Vif protein prevents the deamination by inducing the degradation of APOBEC3G and APOBEC3F. We report here that two additional APOBEC3 family members, APOBEC3B and APOBEC3C, have potent antiviral activity against simian immunodeficiency virus (SIV), but not HIV-1. Both enzymes were encapsidated in HIV-1 and SIV virions and were active against ⌬vif SIV mac and SIV agm . SIV Vif neutralized the antiviral activity of APOBEC3C, but not that of APOBEC3B. APOBEC3B induced abundant G 3 A mutations in both wild-type and ⌬vif SIV reverse transcripts. APOBEC3C induced substantially fewer mutations. APOBEC3F was found to be active against SIV and sensitive to SIV mac Vif. These findings raise the possibility that the different APOBEC3 family members function to neutralize specific lentiviruses.

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Section: Hiv-1 and Siv Encapsidate Apobec3b And Apobec3c-mentioning

confidence: 99%

APOBEC3B and APOBEC3C Are Potent Inhibitors of Simian Immunodeficiency Virus Replication

Chen

König

et al. 2004

Journal of Biological Chemistry

274

276

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“…Understanding the mechanisms involved in these host-virus interactions could lead to important insights into barriers to the zoonotic transmission of pathogenic viruses, mechanisms of virus-host coevolution, and novel antiviral treatment strategies with targeted efforts to restore the natural host defenses. Members of the human apolipoprotein B mRNAediting enzyme catalytic polypeptide-like 3 (APOBEC3 [A3]) family of proteins are potent cellular restriction factors that provide a defense against viral infection by incorporating into virions and targeting nascent viral DNA for deamination of cytidine residues to uridines (1)(2)(3)(4)(5)(6)(7)(8); cytidine deamination of the viral DNA leads to lethal hypermutation of the targeted virus. However, both HIV-1 and HIV-2 have accessory proteins, called viral infectivity factors (Vifs), that can bind to the APOBEC3 proteins to promote their ubiquitination and subsequent proteosomal degradation (9)(10)(11)(12)(13)(14)(15)(16)(17)(18), thereby suppressing their virion incorporation.…”

mentioning

confidence: 99%

HIV-1 and HIV-2 Vif Interact with Human APOBEC3 Proteins Using Completely Different Determinants

Smith

Izumi

Borbet

et al. 2014

J Virol

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Human APOBEC3 (A3) restriction factors provide intrinsic immunity against zoonotic transmission of pathogenic viruses. A3D, A3F, A3G, and A3H haplotype II (A3H-hapII) can be packaged into virion infectivity factor (Vif)-deficient HIVs to inhibit viral replication. To overcome these restriction factors, Vif binds to the A3 proteins in viral producer cells to target them for ubiquitination and proteasomal degradation, thus preventing their packaging into assembling virions. Therefore, the Vif-A3 interactions are attractive targets for novel drug development. HIV-1 and HIV-2 arose via distinct zoonotic transmission events of simian immunodeficiency viruses from chimpanzees and sooty mangabeys, respectively, and Vifs from these viruses have limited homology. To gain insights into the evolution of virus-host interactions that led to successful cross-species transmission of lentiviruses, we characterized the determinants of the interaction between HIV-2 Vif (Vif2) with human A3 proteins and compared them to the previously identified HIV-1 Vif (Vif1) interactions with the A3 proteins. We found that A3G, A3F, and A3H-hapII, but not A3D, were susceptible to Vif2-induced degradation. Alanine-scanning mutational analysis of the first 62 amino acids of Vif2 indicated that Vif2 determinants important for degradation of A3G and A3F are completely distinct from these regions in Vif1, as are the determinants in A3G and A3F that are critical for Vif2-induced degradation. These observations suggest that distinct Vif-A3 interactions evolved independently in different SIVs and their nonhuman primate hosts and conservation of the A3 determinants targeted by the SIV Vif proteins resulted in successful zoonotic transmission into humans. IMPORTANCEPrimate APOBEC3 proteins provide innate immunity against invading pathogens, and Vif proteins of primate lentiviruses have evolved to overcome these host defenses by interacting with them and inducing their proteasomal degradation. HIV-1 and HIV-2 are two human pathogens that induce AIDS, and elucidating interactions between their Vif proteins and human A3 proteins could facilitate the development of novel antiviral drugs. Furthermore, understanding Vif-A3 interactions can provide novel insights into the cross-species transmission events that led to the HIV-1 and HIV-2 pandemics and evolution of host-virus interactions. We carried out mutational analysis of the N-terminal 62 amino acids of HIV-2 Vif (Vif2) and analyzed A3G/A3F chimeras that retained antiviral activity to identify the determinants of the Vif2 and A3 interaction. Our results show that the Vif2-A3 interactions are completely different from the Vif1-A3 interactions, suggesting that these interactions evolved independently and that conservation of the A3 determinants resulted in successful zoonotic transmission into humans.

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“…A3G appears to selectively target single-stranded DNA (27,28) and yields dC to dU mutations in the viral minus-strand DNA formed during reverse transcription (RT) (5, 29 -32). These uracil-containing DNA molecules are either degraded, probably by DNA repair enzymes such as uracil DNA glycosylase (33) and apurinic-apyrimidinic endonucleases, or serve as templates for the synthesis of plus-strand DNA, yielding dG to dA hypermutated proviruses encoding altered proteins.…”

Section: Mutagenesis By Virion-incorporated Apobec3gmentioning

confidence: 99%

APOBEC3 Cytidine Deaminases: Distinct Antiviral Actions along the Retroviral Life Cycle

Chiu

Greene

2006

Journal of Biological Chemistry

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The field of human immunodeficiency virus (HIV) biology has been galvanized by the discovery of innate APOBEC3 cytidine deaminases, which pose powerful barriers to the replication of HIV and other retroviruses. Rapid progress has been made in defining their action, intriguing regulation within cells, expanded range of retroviral targets, and counterstrikes utilized by retroviruses against them. Although scientifically fascinating, advances in APOBEC3 biology may lead to new antiviral drugs and improved lentiviral vectors for gene therapy.

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APOBEC3G is a single-stranded DNA cytidine deaminase and functions independently of HIV reverse transcriptase

Cited by 194 publications

References 58 publications

APOBEC3B and APOBEC3C Are Potent Inhibitors of Simian Immunodeficiency Virus Replication

APOBEC3B and APOBEC3C Are Potent Inhibitors of Simian Immunodeficiency Virus Replication

HIV-1 and HIV-2 Vif Interact with Human APOBEC3 Proteins Using Completely Different Determinants

APOBEC3 Cytidine Deaminases: Distinct Antiviral Actions along the Retroviral Life Cycle

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