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.

Well known alphaviruses include Sindbis, Semliki Forest, chikungunya which is now causing human joint pains and fever in parts of the world where its mosquito host was not previously present, and Ross River virus. Alphaviruses were thought to encode just 9 proteins and there was a 20-year dilemma about one of them, '6K'. Its migration as a doublet on gels was ascribed to different degrees of acylation. The enigma was resolved with the surprising discovery that one member of the doublet, a virion components, was a completely distinct protein TF ('TransFrame'), derived from −1 ribosomal frameshifting (137) . The C-terminal one third of TF encoded by the −1 frame is hydrophilic in contrast to the hydrophobic C-terminus of the '6K' product of standard decoding. TF has a significant function as in a mouse neuropathogenesis model, the mortality of virus with mutant frameshift product was <15% compared to 95% with animal infected with WT virus (138) , and another mouse study has also shown substantial effects (139) . Evolutionary selection for efficient frameshifting for the synthesis of TF has resulted in a remarkable diversity of stimulatory signals (140) .