PLX273675

GSE85474: RNA-dependent RNA polymerase sequence specificities of capsnatching viruses are tailored to aid viral replication

• Organsim human
• Type RNASEQ
• Target gene
• Project ARCHS4

Influenza A virus (IAV) is a major respiratory pathogen that causes severe illness and mortality worldwide. IAV critically depends on host factors for multiple functions that are not encoded by the viral genome. Notably, the IAV RNA-dependent RNA polymerase (RdRP) complex lacks intrinsic 7-methylguanosine (m7G) capping activity and instead snatches the 5m7G caps and the adjacent 10-15nts of host transcripts to prime viral mRNA production, allowing viral transcripts to be recognized by the host translation machinery. We developed a new approach to simultaneously assay the 5 ends of host and viral transcripts in infected cells and identify the host capsnatch origins for viral mRNAs. We used this technique to study the progression of IAV infection in nuclear and cytoplasmic compartiments and determined that the RdRP complex has specific sequence preferences that results in preferential capsnatching and avoidance of sub-populations of host RNAs, which can be reverted by the addition of a cap-snatch inhibitor. Notably, genes avoided by CapSnatch Seq have biological functions enriched for mRNA processing, translation, and viral replication. This selectivity and functional enrichment of avoided genes is conserved among capsnatching viruses including Influenza B Virus and Lymphocytic Choriomeningitis Virus, despite differences in RdRP domains and subcellular locations of RNA substrates. This suggests that this preference convergently arose as a viral strategy to allow cap-snatching viruses to avoid targeting genes necessary for its own replication. SOURCE: Romain FenouilHVB Mount Sinai Hospital