Deeper look into viruses: replication intermediates do code!

Abstract

It is quite intriguing how viruses with their limited coding ability are able to infect their hosts. Processes like RNA editing, transcriptional slippage, RNA splicing, programmed ribosome frameshifting, ribosomal leaky scanning, translational initiation from non-AUG codons, alternative splicing and several other mechanisms greatly expand the coding capacity of viruses, resulting in a more diverse transcriptome and proteome which is conventionally predicted from the ORFs (Ho et al. 2021). Several studies have highlighted that viruses encode various small ORFs that play important roles in viral lifecycle and infection (Gong et al. 2021; Shi et al. 2023). Positive-sense single-stranded RNA (+ ssRNA) viruses have a RNA genome that can act as mRNA and can be translated directly (Louten 2016). These viruses synthesize an −RNA strand which has been long believed to be a replication intermediate without coding ability that serves as a template for synthesizing more + ssRNA strands. However, some studies have highlighted that −RNA replication intermediates do have coding ability expanding the transcriptome of such viruses (Dinan et al. 2020; Retallack et al. 2021; Zhang et al. 2023; Gong et al. 2023).