Foamy Virus Bet Proteins Function as Novel Inhibitors of the APOBEC3 Family of Innate Antiretroviral Defense Factors

Russell, Rebecca A.; Wiegand, Heather L.; Moore, Michael D.; Schäfer, Alexandra; McClure, Myra O.; Cullen, Bryan R.

doi:10.1128/jvi.79.14.8724-8731.2005

Cited by 164 publications

(182 citation statements)

References 48 publications

(115 reference statements)

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“…PFV Bet appears to function as the foamy virus analogue of HIV-1 Vif preventing the incorporation of the human A3G/A3F proteins into progeny virions. However, Bet does not deplete human A3G/A3F in virion producer cells (35). Similar findings have emerged in studies of a distantly related feline foamy virus (34).…”

Section: Counterstrikes By Other Susceptible Virusessupporting

confidence: 67%

“…The 3Ј regions in the minus-strand remain single-stranded for the longest time as they await plus-strand synthesis. This antiviral activity of human A3G also extends to other lentiviruses including simian immunodeficiency virus (SIV), equine infectious anemia virus (EIAV), and even distantly related retroviruses such as murine leukemia virus (MLV) and foamy viruses (6,29,31,34,35) Other Antiviral APOBEC3 Proteins Intriguingly, other APOBEC3 family members also exert antiviral activity. A3F induces dG to dA transitions in viral plus-strand DNAs, and its action is blocked by HIV-1 Vif (18, 36 -38).…”

Section: Mutagenesis By Virion-incorporated Apobec3gmentioning

confidence: 99%

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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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Section: Counterstrikes By Other Susceptible Virusessupporting

confidence: 67%

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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“…HTLV-1 provides the first clear example of a virus that evades hA3G by a cis-acting exclusion mechanism. In contrast, other retroviruses evade hA3G by expressing transacting factors, such as HIV-1 Vif (23-28) or primate foamy virus Bet proteins (8). A previous study indicated that HTLV-1 resists G-to-A hypermutation elicited by hA3G (10).…”

Section: Discussionmentioning

confidence: 99%

“…Human APOBEC3G (hA3G) belongs to a family of cytidine deaminases and is a broadly acting antiviral restriction factor (1,2). In addition to inhibiting the replication of Vif-deficient HIV-1, hA3G has been shown to inhibit the replication of other exogenous retroviruses, endogenous retroviruses, retrotransposons, and hepatitis B virus (3)(4)(5)(6)(7)(8)(9)(10)(11)(12).…”

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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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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“…In contrast to the well-characterized A3-Vif interaction, still little is known about A3-neutralizing strategies used by retroviruses that do not encode a Vif protein. It has been reported that foamy retroviruses use the accessory protein Bet, and Human T-cell leukemia virus type I has evolved a unique nucleocapsid protein to counteract the packaging of cognate A3 proteins (12,44,58,71). The debate over the mechanism of resistance to murine A3 (muA3) of the rodent gammaretrovirus Moloney murine leukemia virus (Mo-MLV) has not come up with a generally convincing model, despite many studies (5, 9, 13, 32, 35, 49).…”

mentioning

confidence: 99%

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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Foamy Virus Bet Proteins Function as Novel Inhibitors of the APOBEC3 Family of Innate Antiretroviral Defense Factors

Cited by 164 publications

References 48 publications

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

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

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

Restriction of Equine Infectious Anemia Virus by Equine APOBEC3 Cytidine Deaminases

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