Functions, structure, and read-through alternative splicing of feline APOBEC3 genes

Münk, Carsten; Beck, Thomas W.; Zielonka, Jörg; Hotz‐Wagenblatt, Agnes; Sarah, Chareza; Marion, Battenberg; Thielebein, Jens; Cichutek, Klaus; Bravo, Ignacio G.; O’Brien, Stephen J.; Löchelt, Martin; Yuhki, Naoya

doi:10.1186/gb-2008-9-3-r48

Cited by 117 publications

(258 citation statements)

References 78 publications

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“…The mouse genome has a single A3 gene, the dog has two, but there are four in cats, six in horses and seven in primates, with the human A3 family all residing within a single 100 kb region on chr22 (A3A, A3B, A3C, A3D, A3F, A3G, A3H). This complexity has arisen from a series of duplications and fusions amongst three ancient clades of A3 genes (A3Z1-A3Z3) established subsequent to the evolution of placental mammals some 100 million years ago (A3 homologs are not found in monotremes or marsupials) [78][79][80]. For instance, the human A3A gene arose from A3Z1, and the human A3B gene arose from fusion of A3Z1 and A3Z2 genes ( Figure I).…”

Section: Box 1: Evolution and Population Variation Within The A3 Genementioning

confidence: 99%

APOBEC3 genes: retroviral restriction factors to cancer drivers

Henderson

Fenton

2015

Trends in Molecular Medicine

104

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Abstract:The APOBEC3 cytosine deaminases play key roles in innate immunity through their ability to mutagenize viral DNA and restrict viral replication. Now recent advances in cancer genomics together with biochemical characterization of the APOBEC3 enzymes have implicated at least two family members in somatic mutagenesis during tumor development. Here we review the evidence linking these enzymes to carcinogenesis and highlight key questions, including the potential mechanisms that misdirect APOBEC3 activity to the host genome, the links to viral infection, and the association between a common APOBEC3 polymorphism and cancer risk. Powered by Editorial Manager® and ProduXion Manager® from Aries Systems CorporationHenderson and Fenton: highlights AbstractThe APOBEC3 cytosine deaminases play key roles in innate immunity through their

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Section: Box 1: Evolution and Population Variation Within The A3 Genementioning

confidence: 99%

APOBEC3 genes: retroviral restriction factors to cancer drivers

Henderson

Fenton

2015

Trends in Molecular Medicine

104

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“…The human A3G and muA3 expression constructs (human A3Z2g-Z1c and muA3Z2-Z3) were provided by N. R. Landau (49). Human A3B, -C, -F, and -H (A3Z2A-Z1b, A3Z2b, A3Z2e-Z2f, and A3Z3); feline A3; and canine A3 expression plasmids were previously described (33,44,57,58). Porcine A3 (A3Z2-Z3) was a gift of Eva Dörrschuck and Ralf Tönjes (GenBank accession no.EU871587; E. Dörrschuck et al, unpublished data).…”

Section: Cells and Transfectionsmentioning

confidence: 99%

“…The evolution of the A3 genes appears as a complex, taxonspecific history of expansion, divergence, selection, and individual extinction of antiviral A3 that parallels in some points the early evolution of placental mammals (38,58). Humans carry seven A3 genes, rodents carry one, pigs carry two, horses carry six, and cats carry four A3 genes (6,31,38,58,63).…”

mentioning

confidence: 99%

“…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%

“…Humans carry seven A3 genes, rodents carry one, pigs carry two, horses carry six, and cats carry four A3 genes (6,31,38,58,63). For the sake of clarity, the nomenclature for nonprimate A3s has been recently changed, based on the characteristics of the zinc (Z)-coordinating domain, to Z1, Z2, and Z3 (37).…”

mentioning

confidence: 99%

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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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Apolipoprotein B mRNA‐editing, catalytic polypeptide cytidine deaminases and retroviral restriction

Koito

Ikeda

2012

WIREs RNA

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Apolipoprotein B (apo B) messenger RNA (mRNA)-editing, catalytic polypeptide (APOBEC) cytidine deaminases (CDAs), which can insert mutations into DNA and/or RNA as a result of their ability to deaminate cytidine (C) to uridine (U), originated from a branch of the zinc-dependent deaminase superfamily at the beginning of vertebrate radiation. The ability of mammalian CDAs encoded by the APOBEC3 genes to restrict a broad number of endogenous retroelements and exogenous retroviruses, including human immunodeficiency virus-1, is well established. Furthermore, APOBEC1 from a variety of mammalian species, which mediates the C-to-U deamination of apo B mRNA, a protein involved in lipid transport, also has a role in controlling mobile elements. A large portion of the mammalian genome is derived from ancient transposable elements. Retroelements, transported by an intracellular copy-and-paste process involving an RNA intermediate, constitute the majority of these mobile genetic elements. Endogenous retroviruses are long-terminal repeat (LTR)-type retroelements that account for approximately 10% of human and murine genomic DNA. Non-LTR members are present in extremely high copy numbers, with approximately 40% of the human and murine genomes consisting of long-interspersed nuclear element-1 (L1). These L1 elements modify mammalian genomes not only through insertions but also by the indirect replication of non-autonomous retrotransposons. As expected, vertebrate intrinsic immunity has evolved to support a balance between retroelement insertions that cause deleterious gene disruptions and those that confer beneficial genetic diversity. This review discusses the current understanding of the mechanism of action of APOBEC CDAs and their role in controlling retroviruses and retroelements.

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Functions, structure, and read-through alternative splicing of feline APOBEC3 genes

Cited by 117 publications

References 78 publications

APOBEC3 genes: retroviral restriction factors to cancer drivers

APOBEC3 genes: retroviral restriction factors to cancer drivers

Restriction of Equine Infectious Anemia Virus by Equine APOBEC3 Cytidine Deaminases

Apolipoprotein B mRNA‐editing, catalytic polypeptide cytidine deaminases and retroviral restriction

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