Translation in Giant Viruses: A Unique Mixture of Bacterial and Eukaryotic Termination Schemes

Abstract

Mimivirus and Megavirus are the best characterized representatives of an expanding new family of giant viruses infecting Acanthamoeba. Their most distinctive features, megabase-sized genomes carried in particles of size comparable to that of small bacteria, fill the gap between the viral and cellular worlds. These giant viruses are also uniquely equipped with genes coding for central components of the translation apparatus. The presence of those genes, thought to be hallmarks of cellular organisms, revived fundamental interrogations on the evolutionary origin of these viruses and the link they might have with the emergence of eukaryotes. In this work, we focused on the Mimivirus-encoded translation termination factor gene, the detailed primary structure of which was elucidated using computational and experimental approaches. We demonstrated that the translation of this protein proceeds through two internal stop codons via two distinct recoding events: a frameshift and a readthrough, the combined occurrence of which is unique to these viruses. Unexpectedly, the viral gene carries an autoregulatory mechanism exclusively encountered in bacterial termination factors, though the viral sequence is related to the eukaryotic/archaeal class-I release factors. This finding is a hint that the virally-encoded translation functions may not be strictly redundant with the one provided by the host. Lastly, the perplexing occurrence of a bacterial-like regulatory mechanism in a eukaryotic/archaeal homologous gene is yet another oddity brought about by the study of giant viruses.

Author Summary

Giant viruses, such as Mimivirus and Megavirus, have huge near-micron-sized particles and possess more genes than several cellular organisms. Furthermore their genomes encode functions not supposed to be in a virus, such as components of the protein translation apparatus. Since Lwoff in 1957, viruses are defined as ultimate obligate intracellular parasites from their need to hijack the peptide synthesis machinery of their host to replicate. We looked at the Mimivirus and Megavirus proteins that recognize the stop codons, the translation termination factors. We found that these genes contain two internal stop codons, meaning that their translation bypasses two distinct stop codons to produce a functional translation termination factor. These types of autoregulatory mechanisms are found in bacterial termination factors, although it involves only a single internal stop codon and not two, and are absent from their eukaryotic and archaeal homologs. Despite these bacterial-like features, giant viruses' termination factors have sequences that do not resemble bacterial genes but are clearly related to the eukaryotic and archaeal termination factors. Thus, giant viruses' termination factors surprisingly combine elements from eukaryotes/archaea and bacteria.