Leaky scanning translation generates a second A49 protein that contributes to vaccinia virus virulence.
Torres, Alice A
The Journal of general virology
Society for General Microbiology
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Neidel, S., Torres, A. A., Ren, H., & Smith, G. (2020). Leaky scanning translation generates a second A49 protein that contributes to vaccinia virus virulence.. The Journal of general virology, 101 (5), 533-541. https://doi.org/10.1099/jgv.0.001386
Vaccinia virus (VACV) strain Western Reserve gene A49L encodes a small, intracellular protein with a Bcl-2 fold that is expressed early during infection and has multiple functions. A49 co-precipitates with the E3 ubiquitin ligase β-TrCP and thereby prevents ubiquitylation and proteasomal degradation of IκBα, and consequently blocks activation of NF-κB. In a similar way, A49 stabilises β-catenin, leading to activation of the wnt signalling pathway. However, a VACV strain expressing a mutant A49 that neither co-precipitates with β-TrCP nor inhibits NF-κB activation, is more virulent than a virus lacking A49, indicating that A49 has another function that also contributes to virulence. Here we demonstrate that gene A49L encodes a second, smaller polypeptide that is expressed via leaky scanning translation from methionine 20 and is unable to block NF-κB activation. Viruses engineered to express either only the large protein or only the small A49 protein both have lower virulence than wild type virus and greater virulence than an A49L deletion mutant. This demonstrates that the small protein contributes to virulence by an unknown mechanism that is independent of NF-κB inhibition. Despite having a large genome with about 200 genes, this study illustrates how VACV makes efficient use of its coding potential and from gene A49L expresses a protein with multiple functions and multiple proteins with different functions.
Animals, Mice, Inbred BALB C, Humans, Mice, Vaccinia virus, Vaccinia, Ubiquitin-Protein Ligases, beta-Transducin Repeat-Containing Proteins, NF-kappa B, Viral Proteins, Virulence, Signal Transduction, Female, Ubiquitination, HEK293 Cells, NF-KappaB Inhibitor alpha
Wellcome Trust (090315/B/09/Z)
WELLCOME TRUST (090315/B/09/A)
External DOI: https://doi.org/10.1099/jgv.0.001386
This record's URL: https://www.repository.cam.ac.uk/handle/1810/300946
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