Why the study?
Viruses evolve strategies to counteract host innate immunity, and ORFV encodes OV20.0 to suppress PKR activation via multiple mechanisms.
The interaction between ORFV OV20.0 and host ADAR1 suppresses RNA editing but enhances viral replication by inhibiting PKR activation, revealing a novel viral evasion strategy.
Identifies ADAR1 as potential ORFV host factor; animal data leave open human relevance and antiviral targeting.
Viruses evolve specific strategies to counteract host innate immunity. ORFV, an important zoonotic pathogen, encodes OV20.0 to suppress PKR activation via multiple mechanisms, including interactions with PKR and two PKR activators. In this study, we demonstrated that OV20.0 interacts with ADAR1, a cellular enzyme responsible for converting adenosine (A) to inosine (I) in RNA. The RNA binding domains, but not the catalytic domain, of ADAR1 are required for this interaction. The OV20.0-ADAR1 association affects the functions of both proteins; OV20.0 suppressed the A-to-I editing of ADAR1, while ADAR1 elevated OV20.0 expression. The proviral role of ADAR1 is likely due to the inhibition of PKR phosphorylation. As RNA editing by ADAR1 contributes to the stability of the genetic code and the structure of RNA, these observations suggest that in addition to serving as a PKR inhibitor, OV20.0 might modulate ADAR1-dependent gene expression to combat antiviral responses or achieve efficient viral infection.
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Liao et al. (2019) studied this question.
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