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Double-stranded-RNA-specific adenosine deaminase 1 (ADAR1) is proposed to contribute to the adaptation of equine infectious anemia virus from horses to donkeys

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Abstract

Equine infectious anemia virus (EIAV) is a member of the genus Lentivirus of the family Retroviridae. Horses are the most susceptible equids to EIAV infection and are therefore the primary hosts of this virus. In contrast, infected donkeys do not develop clinically active equine infectious anemia (EIA). This phenomenon is similar to what has been observed with HIV-1, which fails to induce AIDS in non-human primates. Interestingly, Shen et al. developed a donkey-tropic pathogenic virus strain (EIAVDV117, DV117) by serially passaging a horse-tropic pathogenic strain, EIAVLN40 (LN40), in donkeys. LN40, which was generated by passaging a field isolate in horses, displayed enhanced virulence in horses but caused no clinical symptoms in donkeys. Infection with DV117 induced acute EIA in nearly 100 % of donkeys. Genomic analysis of DV117 revealed a significantly higher frequency of A-to-G substitutions when compared to LN40. Furthermore, detailed analysis of dinucleotide editing showed that A-to-G mutations had a preference for 5’TpA and 5’ApA. These results strongly implicated the activity of the adenosine deaminase, ADAR1, in this type of mutation. Further investigation demonstrated that overexpression of donkey ADAR1 increased A-to-G mutations within the genome of EIAV. Together with our previous finding that multiple mutations in multiple genes are generated in DV117 during its adaptation from horses to donkeys, the present study suggests that ADAR1-induced A-to-G mutations occur during virus adaption to related new hosts contributing to the alteration of EIAV host tropism.

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Acknowledgments

This study was supported by grants from the Chinese National Key Programs for Infectious Diseases (2012ZX10001-008) and the National Natural Science Foundation of China (31070809) to J-H Z.

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Author notes

  1. Jian-Hua Zhou

    Present address: Harbin Pharmaceutical Group Biovaccine Company, Harbin, 150069, China

Authors and Affiliations

  1. State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, 150001, China

    Yan-Dong Tang, **ang Zhang, Lei Na, Xue-feng Wang, Li-Hua Fu, Chun-Hui Zhu, **aojun Wang & Jian-Hua Zhou

  2. Reproductive Medicine Center, Subei People’s Hospital of Jiangsu Province (Clinic Medical College of Yang Zhou University), Yangzhou, 225001, China

    Chun-Hui Zhu

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Correspondence to **aojun Wang or Jian-Hua Zhou.

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Funding

This study was funded by Chinese National Key Programs for Infectious Diseases (grant number 2012ZX10001-008) and the National Natural Science Foundation of China (grant number 31070809).

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The authors declare that they have no conflict of interest.

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This article does not contain any studies with human participants or animals performed by any of the authors.

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Y.-D. Tang and X. Zhang contributed equally to this article.

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Tang, YD., Zhang, X., Na, L. et al. Double-stranded-RNA-specific adenosine deaminase 1 (ADAR1) is proposed to contribute to the adaptation of equine infectious anemia virus from horses to donkeys. Arch Virol 161, 2667–2672 (2016). https://doi.org/10.1007/s00705-016-2951-3

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