4.5 Article

ADAR Editing in Viruses: An Evolutionary Force to Reckon with

Journal

GENOME BIOLOGY AND EVOLUTION
Volume 13, Issue 11, Pages -

Publisher

OXFORD UNIV PRESS
DOI: 10.1093/gbe/evab240

Keywords

RNA editing; adenosine deaminases acting on RNA (ADAR) editing; viral molecular evolution; A-to-I editing; immune response; interferon; RNA viruses; Zika virus; SARS-CoV-2

Funding

  1. Brain Health Research Institute Pilot Award
  2. Healthy Communities Research Initiative Launch Pad Award from Kent State University
  3. National Institutes of Health (National Institute on Aging) [R21AG064479-01, RF1AG054654]

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ADARs are RNA editing enzymes that play a key role in regulating transcriptome and proteome diversity, particularly in viral infections. The impact of ADAR editing on viral replication should be viewed on a spectrum rather than a binary scale, with the position of a virus on this spectrum being highly dependent on various factors. Further research is needed to understand the dynamic factors influencing virus-ADAR interactions and viral evolution.
Adenosine Deaminases that Act on RNA (ADARs) are RNA editing enzymes that play a dynamic and nuanced role in regulating transcriptome and proteome diversity. This editing can be highly selective, affecting a specific site within a transcript, or nonselective, resulting in hyperediting. ADAR editing is important for regulating neural functions and autoimmunity, and has a key role in the innate immune response to viral infections, where editing can have a range of pro- or antiviral effects and can contribute to viral evolution. Here we examine the role of ADAR editing across a broad range of viral groups. We propose that the effect of ADAR editing on viral replication, whether pro- or antiviral, is better viewed as an axis rather than a binary, and that the specific position of a given virus on this axis is highly dependent on virus- and host-specific factors, and can change over the course of infection. However, more research needs to be devoted to understanding these dynamic factors and how they affect virus-ADAR interactions and viral evolution. Another area that warrants significant attention is the effect of virus-ADAR interactions on host-ADAR interactions, particularly in light of the crucial role of ADAR in regulating neural functions. Answering these questions will be essential to developing our understanding of the relationship between ADAR editing and viral infection. In turn, this will further our understanding of the effects of viruses such as SARS-CoV-2, as well as many others, and thereby influence our approach to treating these deadly diseases.

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