Recent studies indicate that many picornavirus genomes contain a second open reading frame translated via diverse non-canonical mechanisms to yield accessory proteins.
This review highlights that picornavirus genomes often contain a second open reading frame translated via non-canonical mechanisms, challenging the single-ORF dogma.
Members of the Picornaviridae family of viruses have single-stranded positive-sense RNA genomes, and are conventionally considered to contain a single open reading frame (ORF) preceded by a long 5′ untranslated region (UTR). The 5′UTR contains an internal ribosomal entry site (IRES) that mediates end-independent initiation of translation of ORF1, resulting in synthesis of a polyprotein that is proteolytically processed to yield the individual structural and nonstructural proteins. However, recent studies indicate that the dogma that picornavirus genomes contain a single ORF (ORF1) is an oversimplification, and that members of many picornavirus genera contain an additional ORF that is translated to yield an accessory protein that may influence pathogenicity and tissue specificity. This review summarizes the structural organization of picornavirus genomes that contain a second ORF. Most commonly, these ORFs overlap the 5′-end of ORF1, but they may also be wholly distinct from ORF1 or located entirely within it in a different reading frame. Ribosomal access to these alternate ORFs has been shown or is hypothesized to depend on a remarkable variety of non-canonical translation mechanisms, including ribosomal recruitment by a second IRES, leaky scanning after IRES-mediated internal ribosomal entry, cap-independent initiation, frame-shifting and termination–reinitiation.
Christopher U.T. Hellen (Mon,) conducted a review in Picornavirus genomes. Recent studies indicate that many picornavirus genomes contain a second open reading frame translated via diverse non-canonical mechanisms to yield accessory proteins.