The artiodactyl APOBEC3 innate immune repertoire shows evidence for a multi-functional domain organization that existed in the ancestor of placental mammals

LaRue, Rebecca S.; Jónsson, S.; Silverstein, Kevin A.T.; Lajoie, Mathieu; Bertrand, Denis; El-Mabrouk, Nadia; Hötzel, Isidro; Andrésdóttir, Valgerður; Smith, Timothy P. L.; Harris, Reuben S.

doi:10.1186/1471-2199-9-104

Cited by 168 publications

(241 citation statements)

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“…Three main clades can be distinguished within the A3 genes, namely A3Z1, A3Z2, and A3Z3. The distribution supports the hypothesis of an ancient origin of the A3 genes in the proto-mammalian genome, followed by early duplication events before the appearance of the main clades within Mammalia (38,58). In this sense, the chromosomal arrangement of the A3 genes in the horse genome is paradigmatic: two copies of the A3Z1 genes, followed by five copies in tandem of the A3Z2 genes, and a single copy of the A3Z3 gene.…”

Section: Discussionsupporting

confidence: 55%

“…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%

“…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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Section: Discussionsupporting

confidence: 55%

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 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

102

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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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“…In particular, the olfactory receptor genes constitute the largest multigene family in verte-brate genomes, with several hundred genes per species [51]. Other examples of TAG families include the APOBEC3 genes [73], the immunoglobulin and T-cell receptor genes [4] and the zinc finger genes [103].…”

Section: Gene Cluster Evolutionmentioning

confidence: 99%

Analysis of Gene Order Evolution Beyond Single-Copy Genes

El-Mabrouk

Sankoff

2012

Methods in Molecular Biology

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The purpose of this chapter is to provide a comprehensive review of the field of genome rearrangement, i.e., comparative genomics based on representation of genomes as ordered sequences of signed genes. We specifically focus on the "hard part" of genome rearrangement, how to handle duplicated genes. The main questions are: how have present-day genomes evolved from a common ancestor? What are the most realistic evolutionary scenarios explaining the observed gene orders? What was the content and structure of ancestral genomes? We aim to provide a concise but complete overview of the field, starting with the practical problem of finding an appropriate representation of a genome as a sequence of ordered genes or blocks, namely the problems of orthology, paralogy and synteny block identification. We then consider three levels of gene organization: the gene family level (evolution by duplication, loss and speciation), the cluster level (evolution by tandem duplications) and the genome level (all types of rearrangement events, including whole genome duplication).

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The artiodactyl APOBEC3 innate immune repertoire shows evidence for a multi-functional domain organization that existed in the ancestor of placental mammals

Cited by 168 publications

References 93 publications

Restriction of Equine Infectious Anemia Virus by Equine APOBEC3 Cytidine Deaminases

Restriction of Equine Infectious Anemia Virus by Equine APOBEC3 Cytidine Deaminases

APOBEC3 genes: retroviral restriction factors to cancer drivers

Analysis of Gene Order Evolution Beyond Single-Copy Genes

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