Characterization of Ribosomal Frameshifting in Theiler's Murine Encephalomyelitis Virus.
(2015) Journal of Virology — Vol. 89, n° 16, p. 8580-8589 (2015)
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- Abstract
- 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.
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Finch, L. K., Ling, R., Napthine, S., Olspert, A., Michiels, T., Lardinois, C., Bell, S., Loughran, G., Brierley, I., & Firth, A. E. (2015). Characterization of Ribosomal Frameshifting in Theiler’s Murine Encephalomyelitis Virus. Journal of Virology, 89(16), 8580-8589. https://doi.org/10.1128/JVI.01043-15 (Original work published 2015)