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Journal of virology2009; 83(15); 7547-7559; doi: 10.1128/JVI.00015-09

Restriction of equine infectious anemia virus by equine APOBEC3 cytidine deaminases.

Abstract: 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.
Publication Date: 2009-05-20 PubMed ID: 19458006PubMed Central: PMC2708611DOI: 10.1128/JVI.00015-09Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The study investigates how certain proteins in the horse genome inhibit certain viruses including the equine infectious anemia virus (EIAV). It also investigates why horses have multiple copies of these antiviral proteins and how these influence their response to different viruses.

Study Overview

  • The researchers focused on a group of proteins known as mammalian APOBEC3 (A3), which are known to prevent infection by retroviruses and retrotransposons – a type of jumping gene that can move around the genome.
  • These proteins are found on chromosome 28 of the horse genome. There are multiple A3 genes present in this region, including two copies of A3Z1, five of A3Z2, and a single copy of A3Z3. This suggested a fascinating evolution of these genes with considerable duplications.

Analyzing Gene Expression and Functionality

  • The research team cloned various equine A3 genes and evaluated their expression and the subcellular location of the related proteins. They also tested these genes’ capabilities to inhibit particular viruses: EIAV, Simian immunodeficiency virus (SIV), and Adeno-associated virus type 2 (AAV-2).
  • The results showed that hematopoietic cells (blood cell producing cells) of horses expressed at least five A3s. Circulating macrophages, a type of white blood cell targeted by EIAV, only expressed part of the A3 repertoire.

Discovering Antiviral Activities and Evolution of A3 Genes

  • They discovered that the five A3Z2 gene copies came about after three consecutive duplications in the horse lineage, following the split between Equidae (horse family) and Carnivora (meat-eating animals).
  • The team noted that the duplicated genes exhibited different antiviral properties against different viruses. For instance, the equine A3Z3 and A3Z2c-Z2d effectively inhibited EIAV, but other A3 genes displayed only weak anti-EIAV activity.
  • The researchers proposed that horse A3 genes may be undergoing a process of subfunctionalization in which each gene adapts to counteract specific viruses. This might offer an evolutionary advantage in maintaining numerous copies of the original gene.

Cite This Article

APA
Zielonka J, Bravo IG, Marino D, Conrad E, Perković M, Battenberg M, Cichutek K, Münk C. (2009). Restriction of equine infectious anemia virus by equine APOBEC3 cytidine deaminases. J Virol, 83(15), 7547-7559. https://doi.org/10.1128/JVI.00015-09

Publication

ISSN: 1098-5514
NlmUniqueID: 0113724
Country: United States
Language: English
Volume: 83
Issue: 15
Pages: 7547-7559

Researcher Affiliations

Zielonka, Jörg
  • Division of Medical Biotechnology, Paul Ehrlich Institut, Langen, Germany.
Bravo, Ignacio G
    Marino, Daniela
      Conrad, Elea
        Perković, Mario
          Battenberg, Marion
            Cichutek, Klaus
              Münk, Carsten

                MeSH Terms

                • APOBEC Deaminases
                • Animals
                • Cell Line
                • Cytidine Deaminase / genetics
                • Cytidine Deaminase / metabolism
                • Cytosine Deaminase / genetics
                • Cytosine Deaminase / metabolism
                • Equine Infectious Anemia / enzymology
                • Equine Infectious Anemia / virology
                • Gene Expression
                • HeLa Cells
                • Horses
                • Humans
                • Infectious Anemia Virus, Equine / genetics
                • Infectious Anemia Virus, Equine / physiology
                • Molecular Sequence Data
                • Multigene Family

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