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.

When the level of S. cerevisiae Ty1 frameshifting was reduced by over-expressing the relevant limiting A-site tRNA, the transposition frequency was greatly reduced (664) . Also when retroviral pol was brought into the same frame as gag, inviability ensued (665) . Early studies on perturbation of HIV gag-pol frameshifting with paromomycin (666), inhibition of human T-cell lymphotropic virus gagpro frameshifting with cycloheximide (667), inhibition of S. cerevisiae double-stranded RNA virus −1 frameshifting by anisomycin and preussin (668, 669) [Addition of anisomycin reduced the −1 frameshifting and toxicity of cells stably transfected with a cassette of disease-associated expanded CAG triplets of spinocerebellar ataxia 3 sequence (374)], and further HIV studies (670-672) were accompanied by numerous comments, including (673-676) on the potential of targeting viral frameshifting. Essential for any such targeting is knowledge of the extent of effects of various levels of frameshift perturbation on virus propagation. This was first systematically investigated with the S. cerevisiae double-stranded RNA virus, L-A (79). In addition to studies on S. cerevisiae Ty elements (677), this was followed by several studies on counterpart significance for several viruses, including Rous sarcoma virus (549) and SARS coronavirus (546, 678, 679) , but especially HIV (660, 680, 681, 676, 682) .