Frog virus 3-mediated translational shut-off: frog virus 3 messages are translationally more efficient than host and heterologous viral messages under conditions of increased translational stress.
Frog virus 3 rapidly and selectively blocks host cell translation while synthesizing more than 60 virus-specific polypeptides. Previous work indicated that virus infection led to activation of a kinase that phosphorylated and, as a consequence, inactivated eIF-2. Although phosphorylation of eIF-2 could explain the rapid decline in host cell translation, it could not explain how viral protein synthesis persisted in the face of host shut-off. To explain this phenomenon, we speculated that viral messages, either as a consequence of their higher translational efficiency or their greater abundance, were able to outcompete host messages for the remaining translational initiation complexes. To test this hypothesis, the relative translational efficiency of three characteristic FV3 messages was measured against that of several model messages. Translational efficiency was determined by monitoring the resistance (and hence the competitiveness) of a given transcript to increasing concentrations of salt in vitro and in vivo. In both rabbit reticulocyte lysates and wheat germ extracts, FV3 messages were more resistant to supra-optimal concentrations of potassium acetate than globin message and three BMV transcripts. In vivo, FV3 polypeptides were synthesized in the presence of salt concentrations that blocked host cell protein synthesis. These results suggest that the selective translation of FV3 messages in virus-infected cells may partly be due to the higher translational efficiency of viral messages. Structural features that contribute to translational efficiency are discussed.
Department of Microbiology, University of Mississippi Medical Center, Jackson 39216-4505.
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D000085:Acetates / Q000494:pharmacology; D019342:Acetic Acid; D000818:Animals; D007497:Iridoviridae / Q000235:genetics*; D009029:Mosaic Viruses / Q000235:genetics; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis*; D011817:Rabbits; D012156:Reticulocytes / Q000187:drug effects / Q000378:metabolism; D012680:Sensitivity and Specificity; D014764:Viral Proteins / Q000096:biosynthesis / Q000235:genetics
D000085:Acetates; D012333:RNA, Messenger; D014764:Viral Proteins; D019342:Acetic Acid