Genetic reprogramming by retroviruses: enhanced suppression of translational termination

Abstract

Viruses often exploit or subvert host machinery for their own purposes during replication. A search for proteins interacting with the murine leukemia virus reverse transcriptase (RT) recently provided a new example of such exploitation. RT was found to bind the eukaryotic translational release factor 1 (eRF1), the protein that recognizes stop codons and, in complex with eRF3, causes termination and polypeptide release from the ribosome. RT is derived from a large Gag-Pol polyprotein, and its synthesis requires a translational readthrough, a suppression of termination, at a stop codon at the end of the gag gene. The binding of eRF1 by RT was found to inhibit eRF1 action, enhance the efficiency of readthrough, and thus cause higher levels of RT synthesis. The observations suggest that retroviruses manipulate the translational machinery in sophisticated ways to fine-tune their own gene expression.