Characterization of Ribosomal Frameshifting in Theiler's Murine Encephalomyelitis Virus

Theiler's murine encephalomyelitis virus (TMEV) is a member of the genus Cardiovirus in the Picornaviridae, a family of positive-sense single-stranded RNA viruses. Previously, we demonstrated that in the related cardiovirus, Encephalomyocarditis virus, a programmed-1 ribosomal frameshift (1 PRF...

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Bibliographic Details
Published in:Journal of virology 2015-08, Vol.89 (16), p.8580-8589
Main Authors: Finch, Leanne K, Ling, Roger, Napthine, Sawsan, Olspert, Allan, Michiels, Thomas, Lardinois, Cécile, Bell, Susanne, Loughran, Gary, Brierley, Ian, Firth, Andew E
Format: Article
Language:English
Subjects:
Animals
Cardiovirus
Cell Line
Encephalomyocarditis virus
Frameshifting, Ribosomal - genetics
Genome and Regulation of Viral Gene Expression
Immunoblotting
Luciferases
Mass Spectrometry
Mice
Mutagenesis
Picornaviridae
Recombination, Genetic - genetics
Rosaniline Dyes
Spotlight
Theiler's encephalomyelitis virus
Theilovirus - genetics
Viral Plaque Assay
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Summary:Theiler's murine encephalomyelitis virus (TMEV) is a member of the genus Cardiovirus in the Picornaviridae, a family of positive-sense single-stranded RNA viruses. Previously, we demonstrated that in the related cardiovirus, Encephalomyocarditis virus, a programmed-1 ribosomal frameshift (1 PRF) occurs at a conserved G_GUU_UUU sequence within the 2B-encoding region of the polyprotein open reading frame (ORF). Here we show that-1 PRF occurs at a similar site during translation of the TMEV genome. In addition, we demonstrate that a predicted 3= RNA stem-loop structure at a noncanonical spacing downstream of the shift site is required for efficient frameshifting in TMEV and that frameshifting also requires virus infection. Mutating the G_GUU_UUU shift site to inhibit frameshifting results in an attenuated virus with reduced growth kinetics and a small-plaque phenotype. Frameshifting in the virus context was found to be extremely efficient at 74 to 82%, which, to our knowledge, is the highest frameshifting efficiency recorded to date for any virus. We propose that highly efficient-1 PRF in TMEV provides a mechanism to escape the confines of equimolar expression normally inherent in the single-polyprotein expression strategy of picornaviruses.
ISSN:0022-538X
1098-5514
DOI:10.1128/JVI.01043-15