Reovirus infection induces transcriptome-wide unique A-to-I editing changes in the murine fibroblasts.

• Reovirus infections primarily occur in infants and young children, with various respiratory, gastrointestinal, and central nervous system symptoms, and may lead to severe meningitis and encephalitis. This study examines the host-side transcriptome-wide consequences of reovirus infection, in order to better understand the impact of viral infection on the host. • Our results show that reovirus infection induces transcriptome-wide RNA editing changes, resulting in nuanced and dynamic shifts in the global editing landscape. These shifts include site-specific unique editing changes, particularly in genes involved in cellular regulation and immunity. • Majority of identified editing changes were observed within 3′UTRs, where these variants can potentially influence gene expression through interruption of micro-RNA binding, polyadenylation, and posttranscriptional processing. The conversion of Adenosine (A) to Inosine (I), by Adenosine Deaminases Acting on RNA or ADARs, is an essential post-transcriptional modification that contributes to proteome diversity and regulation in metazoans including humans. In addition to its transcriptome-regulating role, ADARs also play a major part in immune response to viral infection, where an interferon response activates interferon-stimulated genes, such as ADARp150, in turn dynamically regulating host-virus interactions. A previous report has shown that infection from reoviruses, despite strong activation of ADARp150, does not influence the editing of some of the major known editing targets, while likely editing others, suggesting a potentially nuanced editing pattern that may depend on different factors. However, the results were based on a handful of selected editing sites and did not cover the entire transcriptome. Thus, to determine whether and how reovirus infection specifically affects host ADAR editing patterns, we analyzed a publicly available deep-sequenced RNA-seq dataset, from murine fibroblasts infected with wild-type and mutant reovirus strains that allowed us to examine changes in editing patterns on a transcriptome-wide scale. To the best of our knowledge, this is the first transcriptome-wide report on host editing changes after reovirus infection. Our results demonstrate that reovirus infection induces unique nuanced editing changes in the host, including introducing sites uniquely edited in infected samples. Genes with edited sites are overrepresented in pathways related to immune regulation, cellular signaling, metabolism, and growth. Moreover, a shift in editing targets has also been observed, where the same genes are edited in infection and control conditions but at different sites, or where the editing rate is increased for some and decreased for other differential targets, supporting the hypothesis of dynamic and condition-specific editing by ADARs. [ABSTRACT FROM AUTHOR]