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

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.