Double-stranded-RNA-specific adenosine deaminase 1 (ADAR1) is proposed to contribute to the adaptation of equine infectious anemia virus from horses to donkeys.
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.
Publication Date: 2016-07-06 PubMed ID: 27383210DOI: 10.1007/s00705-016-2951-3Google Scholar: Lookup The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Journal Article
Summary
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The research suggests that the enzyme ADAR1 plays a critical role in adapting equine infectious anemia virus (EIAV) from horses, its original hosts, to donkeys.
Overview of the Research
- The research paper focuses on the phenomenon of EIAV adaptation from horses to donkeys. While EIAV causes infectious anemia in horses, the primary hosts, it has been observed to cause no clinical symptoms in infected donkeys. This adaptation is similar to HIV-1, which doesn’t cause AIDS in non-human primates.
- This observation sparked an interest in understanding the underlying mechanism allowing this adaptation. The researchers highlighted the activity of an enzyme, ADAR1, in enabling this transition.
Processing and Analysis
- Shen et al. managed to develop a donkey-tropic pathogenic virus strain, EIAVDV117, that induced acute EIA in almost 100% of donkeys. They did so by repeatedly passaging a horse-tropic pathogenic strain, EIAVLN40, in donkeys.
- A detailed genomic analysis of EIAVDV117 against EIAVLN40 revealed a higher frequency of A-to-G (adenine to guanine) substitutions.
- The A-to-G mutations showed a preference for certain dinucleotide configurations, such as 5’TpA and 5’ApA, which highly hinted at the enzymatic activity of ADAR1.
Role of ADAR1 in Virus Adaptation
- ADAR1 is a double-stranded-RNA-specific adenosine deaminase, an enzyme known for changing adenine into inosine, a process that can be read as guanine.
- The research team proceeded to overexpress the donkey version of ADAR1 and found this led to increased A-to-G mutations within EIAV’s genome.
- A link between ADAR1 activity and the adaptation of EIAV to new hosts was thus established. ADAR1-induced A-to-G mutations were suggested to contribute to altering EIAV’s host preference, changing it from being primarily horse-orientated to be able to cause disease in donkeys successfully.
This study provides a significant insight about the possible mechanism of viral host adaptation, and can pave the way for future research in virus evolution and cross-species transmission.
Cite This Article
APA
Tang YD, Zhang X, Na L, Wang XF, Fu LH, Zhu CH, Wang X, Zhou JH.
(2016).
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(10), 2667-2672.
https://doi.org/10.1007/s00705-016-2951-3 Publication
Researcher Affiliations
- State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, 150001, China.
- State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, 150001, China.
- State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, 150001, China.
- State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, 150001, China.
- State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, 150001, China.
- State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, 150001, China.
- Reproductive Medicine Center, Subei People's Hospital of Jiangsu Province (Clinic Medical College of Yang Zhou University), Yangzhou, 225001, China.
- State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, 150001, China. xjw@hvri.ac.cn.
- State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, 150001, China. jianhua_uc@126.com.
- Harbin Pharmaceutical Group Biovaccine Company, Harbin, 150069, China. jianhua_uc@126.com.
MeSH Terms
- Adaptation, Biological
- Adenosine Deaminase / metabolism
- Animals
- Equidae
- Horses
- Infectious Anemia Virus, Equine / genetics
- Infectious Anemia Virus, Equine / pathogenicity
- Point Mutation
- RNA, Double-Stranded / metabolism
- Sequence Analysis, DNA
- Serial Passage
Citations
This article has been cited 7 times.- Wang XF, Zhang X, Ma W, Li J, Wang X. Host cell restriction factors of equine infectious anemia virus.. Virol Sin 2023 Aug;38(4):485-496.
- Zhu T, Niu G, Zhang Y, Chen M, Li CY, Hao L, Zhang Z. Host-mediated RNA editing in viruses.. Biol Direct 2023 Mar 28;18(1):12.
- Piontkivska H, Wales-McGrath B, Miyamoto M, Wayne ML. ADAR Editing in Viruses: An Evolutionary Force to Reckon with.. Genome Biol Evol 2021 Nov 5;13(11).
- Cu00e2mara RJF, Bueno BL, Resende CF, Balasuriya UBR, Sakamoto SM, Reis JKPD. Viral Diseases that Affect Donkeys and Mules.. Animals (Basel) 2020 Nov 25;10(12).
- Dong J, Rao D, Ding Y, Zhao Y, Zhang G, Deng K, Liu T, Jiao F, Hu J, Wang H, Zhang N, Zhao P, Leng C. Hypermutations in porcine respiratory and reproductive syndrome virus.. Can J Vet Res 2019 Apr;83(2):104-109.
- de Pablo-Maiso L, Domu00e9nech A, Echeverru00eda I, Gu00f3mez-Arrebola C, de Andru00e9s D, Rosati S, Gu00f3mez-Lucia E, Reina R. Prospects in Innate Immune Responses as Potential Control Strategies against Non-Primate Lentiviruses.. Viruses 2018 Aug 17;10(8).
- Wang HN, Rao D, Fu XQ, Hu MM, Dong JG. Equine infectious anemia virus in China.. Oncotarget 2018 Jan 2;9(1):1356-1364.