Human APOBEC3F Is Another Host Factor That Blocks Human Immunodeficiency Virus Type 1 Replication

Zheng, Yong Hui; Irwin, Dan; Kurosu, Takeshi; Tokunaga, Kenzo; Sata, Tetsutaro; Peterlin, B. Matija

doi:10.1128/jvi.78.11.6073-6076.2004

Cited by 411 publications

(408 citation statements)

References 38 publications

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“…Consistent with this hypothesis, it was recently shown that nonfunctional human A3Z3 alleles are highly prevalent and have been actively selected for (24,62). The discovery of the cellular antiviral cytidine deaminase A3G in search for the Vif cofactor explained many in vitro observations regarding the replication of HIV-1 and HIV-1 ⌬vif in specific human cells (5,49,78,91,100). It also contributed to explain the narrow host range of HIV-1 that shows spreading replication only in humans and chimpanzees (49,59).…”

Section: Discussionmentioning

confidence: 56%

Restriction of Equine Infectious Anemia Virus by Equine APOBEC3 Cytidine Deaminases

Zielonka

Bravo²,

Marino

et al. 2009

J Virol

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The mammalian APOBEC3 (A3) proteins comprise a multigene family of cytidine deaminases that act as potent inhibitors of retroviruses and retrotransposons. The A3 locus on the chromosome 28 of the horse genome contains multiple A3 genes: two copies of A3Z1, five copies of A3Z2, and a single copy of A3Z3, indicating a complex evolution of multiple gene duplications. We have cloned and analyzed for expression the different equine A3 genes and examined as well the subcellular distribution of the corresponding proteins. Additionally, we have tested the functional antiretroviral activity of the equine and of several of the human and nonprimate A3 proteins against the Equine infectious anemia virus (EIAV), the Simian immunodeficiency virus (SIV), and the Adeno-associated virus type 2 (AAV-2). Hematopoietic cells of horses express at least five different A3s: A3Z1b, A3Z2a-Z2b, A3Z2c-Z2d, A3Z2e, and A3Z3, whereas circulating macrophages, the natural target of EIAV, express only part of the A3 repertoire. The five A3Z2 tandem copies arose after three consecutive, recent duplication events in the horse lineage, after the split between Equidae and Carnivora. The duplicated genes show different antiviral activities against different viruses: equine A3Z3 and A3Z2c-Z2d are potent inhibitors of EIAV while equine A3Z1b, A3Z2a-Z2b, A3Z2e showed only weak anti-EIAV activity. Equine A3Z1b and A3Z3 restricted AAV and all equine A3s, except A3Z1b, inhibited SIV. We hypothesize that the horse A3 genes are undergoing a process of subfunctionalization in their respective viral specificities, which might provide the evolutionary advantage for keeping five copies of the original gene.The Equine infectious anemia virus (EIAV) (family Retroviridae, genus Lentivirus) infects equids almost worldwide, causing a persistent infection characterized by recurring viremia, fever, thrombocytopenia, and wasting symptoms (40). EIAV infections are used as a model for natural immunologic control of lentivirus replication and virus persistence and as a test system to improve vaccines against lentiviruses (10,40,41,82). In vivo EIAV replicates predominantly in macrophages (77). Interaction with the equine lentiviral receptor 1 (ELR1) has been demonstrated to be responsible for EIAV internalization (96). There have been no reported cases of EIAV infections in humans, suggesting that it is an intrinsically safe virus and of interest for use in a clinical setting. Therefore, EIAV-based lentiviral vectors for human gene therapy were recently developed (1, 67, 68).In the last few years, two cellular proteins that inhibit many different retroviruses have been characterized: tripartite motif protein 5 alpha (TRIM5␣) and apolipoprotein B mRNAediting enzyme-catalytic polypeptide 3 (APOBEC3 [A3]) (for a review, see reference 92). With respect to TRIM5␣ proteins, both human and nonhuman primate TRIM5␣ orthologues can restrict infection by EIAV (26,72). The activity of equine TRIM5␣ on EIAV infection, however, has not been described so far. With respect to A3 proteins...

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Section: Discussionmentioning

confidence: 56%

Restriction of Equine Infectious Anemia Virus by Equine APOBEC3 Cytidine Deaminases

Zielonka

Bravo²,

Marino

et al. 2009

J Virol

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“…As with A3G, A3F also induces G-to-A hypermutation, though the degree of mutagenesis has been noted to be lower than for A3G in some cultured cell experiments (Bishop et al 2004a;Zheng et al 2004;Zennou & Bieniasz 2006;Holmes et al 2007a). The consensus dinucleotide target for deamination is also different with 5 0 -TC (substrate cytidine underlined) serving as the preferred site for A3F (Bishop et al 2004a;Liddament et al 2004;Wiegand et al 2004), rather than the 5 0 -CC defined for A3G ( §5).…”

Section: Anti-hiv-1 Phenotypes Of Diverse Human Apobec Proteinsmentioning

confidence: 99%

“…Accordingly, multiple groups have examined the anti-HIV-1 properties of all the APOBEC proteins, and the results have been catalogued in recent review papers (Holmes et al 2007b;Chiu & Greene 2008). The most significant other human protein with respect to HIV-1 is APOBEC3F (A3F): it is a strong inhibitor of vifdeficient HIV-1, though not as potent as A3G (Bishop et al 2004a;Liddament et al 2004;Wiegand et al 2004;Zheng et al 2004;Zennou & Bieniasz 2006), and is the family member that is most closely related to A3G in that they share approximately 50 per cent sequence identity. A3F is also efficiently inhibited by HIV-1 Vif via the recruitment of the cullin5-elongin B/C-Rbx ubiquitin ligase and ensuing proteasomal degradation .…”

Section: Anti-hiv-1 Phenotypes Of Diverse Human Apobec Proteinsmentioning

confidence: 99%

APOBEC proteins and intrinsic resistance to HIV-1 infection

Malim

2008

Phil. Trans. R. Soc. B

239

258

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Members of the APOBEC family of cellular polynucleotide cytidine deaminases, most notably APOBEC3G and APOBEC3F, are potent inhibitors of HIV-1 infection. Wild type HIV-1 infections are largely spared from APOBEC3G/F function through the action of the essential viral protein, Vif. In the absence of Vif, APOBEC3G/F are encapsidated by budding virus particles leading to excessive cytidine (C) to uridine (U) editing of negative sense reverse transcripts in newly infected cells. This registers as guanosine (G) to adenosine (A) hypermutations in plus-stranded cDNA. In addition to this profoundly debilitating effect on genetic integrity, APOBEC3G/F also appear to inhibit viral DNA synthesis by impeding the translocation of reverse transcriptase along template RNA. Because the functions of Vif and APOBEC3G/F proteins oppose each other, it is likely that fluctuations in the Vif–APOBEC balance may influence the natural history of HIV-1 infection, as well as viral sequence diversification and evolution. Given Vif's critical role in suppressing APOBEC3G/F function, it can be argued that pharmacologic strategies aimed at restoring the activity of these intrinsic anti-viral factors in the context of infected cells in vivo have clear therapeutic merit, and therefore deserve aggressive pursuit.

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“…In the absence of the human immunodeficiency virus type 1 (HIV-1) accessory protein Vif, hA3F and hA3G are incorporated into virions and induce G-to-A hypermutations in the viral genome (1,8,12,14,27,29,30). Vif counteracts hA3F and hA3G by preventing their encapsidation within virions and by inducing their proteasomal degradation (4,11,13,16,17,24,25,28).…”

mentioning

confidence: 99%

APOBEC3F and APOBEC3G mRNA Levels Do Not Correlate with Human Immunodeficiency Virus Type 1 Plasma Viremia or CD4 ⁺ T-Cell Count

Cho¹,

Drechsler

Burke

et al. 2006

J Virol

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APOBEC3F and APOBEC3G (hA3F and hA3G) are part of an innate mechanism of antiretroviral defense. The human immunodeficiency virus type 1 (HIV-1) accessory protein Vif targets both proteins for proteasomal degradation. Using mRNA from peripheral blood mononuclear cells of 92 HIV-infected subjects not taking antiretroviral therapy and 19 HIV-uninfected controls, we found that hA3F (P < 0.001) and hA3G (P ‫؍‬ 0.016) mRNA levels were lower in HIV-infected subjects and were positively correlated with one another (P ‫؍‬ 0.003). However, we found no correlation in the abundance of either hA3F or hA3G mRNA with either viral load or CD4 counts in HIV-infected subjects.

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Human APOBEC3F Is Another Host Factor That Blocks Human Immunodeficiency Virus Type 1 Replication

Cited by 411 publications

References 38 publications

Restriction of Equine Infectious Anemia Virus by Equine APOBEC3 Cytidine Deaminases

Restriction of Equine Infectious Anemia Virus by Equine APOBEC3 Cytidine Deaminases

APOBEC proteins and intrinsic resistance to HIV-1 infection

APOBEC3F and APOBEC3G mRNA Levels Do Not Correlate with Human Immunodeficiency Virus Type 1 Plasma Viremia or CD4 ⁺ T-Cell Count

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Human APOBEC3F Is Another Host Factor That Blocks Human Immunodeficiency Virus Type 1 Replication

Cited by 411 publications

References 38 publications

Restriction of Equine Infectious Anemia Virus by Equine APOBEC3 Cytidine Deaminases

Restriction of Equine Infectious Anemia Virus by Equine APOBEC3 Cytidine Deaminases

APOBEC proteins and intrinsic resistance to HIV-1 infection

APOBEC3F and APOBEC3G mRNA Levels Do Not Correlate with Human Immunodeficiency Virus Type 1 Plasma Viremia or CD4 + T-Cell Count

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APOBEC3F and APOBEC3G mRNA Levels Do Not Correlate with Human Immunodeficiency Virus Type 1 Plasma Viremia or CD4 ⁺ T-Cell Count