Scientific Publications by FDA Staff
J Virol 2010 May;84(9):4330-40
Achieving a Golden Mean: Mechanisms by Which Coronaviruses Ensure Synthesis of the Correct Stoichiometric Ratios of Viral Proteins.
Plant EP, Rakauskaite R, Taylor DR, Dinman JD
In retroviruses and the dsRNA totiviruses, the efficiency of programmed -1 ribosomal frameshifting is critical for ensuring the proper ratios of upstream encoded capsid proteins to downstream encoded replicase enzymes. The genomic organizations of many other frameshifting viruses, including the coronaviruses, are very different in that their upstream open reading frames encode nonstructural proteins, the frameshift-dependent downstream open reading frames encode enzymes involved in transcription and replication, while their structural proteins are encoded by subgenomic mRNAs. The biological significance of frameshifting efficiency and how the relative ratios of proteins encoded by the upstream and downstream open reading frames affect virus propagation has heretofore not been explored. Here, three different strategies were employed to test the hypothesis that the -1 PRF signals of coronaviruses have evolved to produce the correct ratios of upstream to downstream encoded proteins. Specifically, infectious clones of the SARS-associated coronavirus harboring mutations that lower frameshift efficiency decreased infectivity by > 4 orders of magnitude. Second, a series of frameshift promoting mRNA pseudoknot mutants was employed to demonstrate that the frameshift signals of the SARS-associated coronavirus and Mouse Hepatitis virus have evolved to promote optimal frameshift efficiencies. Last, we show that a previously described "frameshift attenuator element" does not actually affect frameshifting per se, but rather serves to limit the fraction of ribosomes available for frameshifting. The findings of these analyses all support a "golden mean" model in which viruses use both programmed ribosomal frameshifting and translational attenuation to control the relative ratios of their encoded proteins.
|Category: Journal Article|
|PubMed ID: #20164235||DOI: 10.1128/JVI.02480-09|
|PubMed Central ID: #PMC2863758|
|Includes FDA Authors from Scientific Area(s): Biologics|
|Entry Created: 2011-10-04||Entry Last Modified: 2012-08-29|