Ribosomal frameshifting and transcriptional slippage: From genetic steganography and cryptography to adventitious use

Atkins, John F.; Loughran, Gary; Bhatt, Pramod R.; Firth, Andrew E.; Baranov, Pavel V.

Many flaviviruses also use −1 frameshifting mediated access to a short ORF overlapping an internal region of their long polyprotein-encoding ORF to generate a transframe encoded protein that is N-terminally coincident with a polyprotein cleavage product. Frameshifting evolved independently on several occasions in flavivirus evolution, though the sites within particular clades are conserved (70, 119) . The Japanese encephalitis serogroup of flaviviruses utilize frameshifting that has significant consequences for viral neuroinvasiveness (120) (121) (122) . Many insect specific flaviviruses also utilize frameshifting in their expression (119, 123, 124) , and some of these flaviviruses have major effects on medically important flaviviruses co-infecting the same mosquito cells. Not only does the frameshifting result in the synthesis of additional functional proteins, in some species it diverts a substantial proportion of ribosomes from synthesizing 3 encoded replicative proteins. This permits quicker recycling of ribosomes for synthesis of further 5 encoded structural proteins, and downregulates polymerase synthesis. However, utilization of frameshifting by certain other groups of flaviviruses including those containing Zika and yellow fever viruses is unknown.