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.

Like cardiovirus frameshifting, virus infection is also required for the newly discovered second site of arterivirus frameshifting (22). A trans-acting viral protein is required for frameshift stimulation (23,133). This frameshifting is in addition to the long known programmed −1 frameshifting that occurs several kilobases 3 of the new frameshift site ( Figure 3C ). The classical site, which was first identified in equine arteritis virus, is at the end of the long 5 coding sequence, ORF1a and frameshifting at it expresses a much longer replicase precursor polyprotein (134, 135) . The newly discovered frameshift site mediates both −1 and −2 frameshifting (22,23). The C-terminal region derived from the new frame after −2 frameshifting is relatively short but does have an alternative transmembrane region and is targeted to a different subcellular compartment. In the economically important pig virus, porcine reproductive and respiratory syndrome virus, inactivation of the −2 frameshift product results in a 50 to 100-fold reduction in replication efficiency in cell culture (22), with the product down-regulating Swine Leukocyte Antigen class I (136) . The ribosomes that shift −1 instead of −2 at the same site, immediately encounter a stop codon and terminate (23).