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Journal of virology2008; 82(23); 11889-11901; doi: 10.1128/JVI.01537-08

Equine infectious anemia virus resists the antiretroviral activity of equine APOBEC3 proteins through a packaging-independent mechanism.

Abstract: Equine infectious anemia virus (EIAV), uniquely among lentiviruses, does not encode a vif gene product. Other lentiviruses, including human immunodeficiency virus type 1 (HIV-1), use Vif to neutralize members of the APOBEC3 (A3) family of intrinsic immunity factors that would otherwise inhibit viral infectivity. This suggests either that equine cells infected by EIAV in vivo do not express active A3 proteins or that EIAV has developed a novel mechanism to avoid inhibition by equine A3 (eA3). Here, we demonstrate that horses encode six distinct A3 proteins, four of which contain a single copy of the cytidine deaminase (CDA) consensus active site and two of which contain two CDA motifs. This represents a level of complexity previously seen only in primates. Phylogenetic analysis of equine single-CDA A3 proteins revealed two proteins related to human A3A (hA3A), one related to hA3C, and one related to hA3H. Both equine double-CDA proteins are similar to hA3F and were named eA3F1 and eA3F2. Analysis of eA3F1 and eA3F2 expression in vivo shows that the mRNAs encoding these proteins are widely expressed, including in cells that are natural EIAV targets. Both eA3F1 and eA3F2 inhibit retrotransposon mobility, while eA3F1 is a potent inhibitor of a Vif-deficient HIV-1 mutant and induces extensive editing of HIV-1 reverse transcripts. However, both eA3F1 and eA3F2 are weak inhibitors of EIAV. Surprisingly, eA3F1 and eA3F2 were packaged into EIAV and HIV-1 virions as effectively as hA3G, although only the latter inhibited EIAV infectivity. Moreover, all three proteins bound both the HIV-1 and EIAV nucleocapsid protein specifically in vitro. It therefore appears that EIAV has evolved a novel mechanism to specifically neutralize the biological activities of the cognate eA3F1 and eA3F2 proteins at a step subsequent to virion incorporation.
Publication Date: 2008-09-25 PubMed ID: 18818324PubMed Central: PMC2583693DOI: 10.1128/JVI.01537-08Google Scholar: Lookup
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  • Journal Article
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  • 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 the equine infectious anemia virus (EIAV) resists antiretroviral activity from horse APOBEC3 proteins and suggests a new mechanism for this resistance that does not rely on protein packaging.

Introduction and Background

  • The research concerns itself with the EIAV, a Lentivirus species similar to HIV-1 (Human Immunodeficiency Virus type 1). Unlike most other Lentiviruses, EIAV does not encode a vif gene, a product that other Lentiviruses use to neutralize A3 proteins, crucial fighters against viral infectivity. This unique factor hints towards two possibilities: either the horses infected with EIAV do not develop active A3 proteins, or EIAV has devised a unique method to prevent inhibition by equine A3 (eA3).

Findings

  • The research shows that horses encode six distinct A3 proteins. Four contain a single copy of the cytidine deaminase (CDA) consensus active site, and two contain two such motifs. This complexity of A3 proteins’ encoding in horses matches that only previously seen in primates. Through phylogenetic analysis, various similarities were found between certain human and equine A3 proteins.
  • The findings also present that the mRNAs conveying these proteins are widely expressed, particularly in cells that EIAV naturally targets. eA3F1, one of the A3 proteins in horses, inhibits a Vif-deficient HIV-1 mutant, influencing the editing of HIV-1 reverse transcripts. Yet, both eA3F1 and its counterpart eA3F2 were found to be weak inhibitors of EIAV.

Conclusion

  • Interestingly, both eA3F1 and eA3F2 were found to be packaged into EIAV and HIV-1 as effectively as a similar human protein (hA3G), despite only the latter being an effective EIAV inhibitor. All three proteins bound both the HIV-1 and EIAV nucleocapsid proteins specifically in vitro.
  • As a result, the paper suggests that EIAV may have evolved a unique method to neutralize the biological activities of eA3F1 and eA3F2. The new mechanism seems to act after virion incorporation, thus moving away from the traditional protein packaging-dependent method.

Cite This Article

APA
Bogerd HP, Tallmadge RL, Oaks JL, Carpenter S, Cullen BR. (2008). Equine infectious anemia virus resists the antiretroviral activity of equine APOBEC3 proteins through a packaging-independent mechanism. J Virol, 82(23), 11889-11901. https://doi.org/10.1128/JVI.01537-08

Publication

ISSN: 1098-5514
NlmUniqueID: 0113724
Country: United States
Language: English
Volume: 82
Issue: 23
Pages: 11889-11901

Researcher Affiliations

Bogerd, Hal P
  • Department of Molecular Genetics and Microbiology and Center for Virology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Tallmadge, Rebecca L
    Oaks, J Lindsay
      Carpenter, Susan
        Cullen, Bryan R

          MeSH Terms

          • APOBEC-1 Deaminase
          • Amino Acid Sequence
          • Animals
          • Chromosome Mapping
          • Cytidine Deaminase / chemistry
          • Cytidine Deaminase / genetics
          • Cytidine Deaminase / physiology
          • HIV-1 / genetics
          • HIV-1 / immunology
          • HeLa Cells
          • Horses / immunology
          • Humans
          • Immunity, Innate
          • Infectious Anemia Virus, Equine / immunology
          • Molecular Sequence Data
          • Protein Structure, Tertiary
          • Retroelements
          • Virus Assembly
          • Virus Replication

          Grant Funding

          • R01 CA128568-01A2 / NCI NIH HHS
          • T32 AI007025 / NIAID NIH HHS
          • R01 CA128568 / NCI NIH HHS
          • R01 AI065301 / NIAID NIH HHS
          • R01-AI065301 / NIAID NIH HHS

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          Citations

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