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How does vaccinia virus downregulate multiple host proteins early after infection?

Supervisor: Professor Geoffrey L Smith
Based at Division of Virology, Tennis Court Road

 

Vaccinia virus (VACV) is the live vaccine used to eradicate smallpox and is being re-engineered as a vaccine for other diseases. VACV replicates in the cytoplasm and encodes about 200 genes of which about half are non-essential for replication but suppress the host immune response to infection. Recently, whole cell proteomics during VACV infection has demonstrated that several groups of cellular proteins that are involved in innate immunity are specifically and rapidly down-regulated after VACV infection. The project will seek to determine how VACV achieves this and what the biological consequences are.

Recent publications

Strnadova, P., Ren, H., Valentine, R., Mazzon, M., Brierley, I. & Smith, G.L. (2015). Inhibition of translation initiation by protein 169: a vacciniavirus strategy to compromise innate and adaptive immunity and alter virus virulence. PLoS Pathogens. 11, e1005151.

Sumner, R.P., Ren, H., Ferguson, B.J. & Smith, G.L. (2016). Increased attenuation but decreased immunogenicity by deletion of multiplevaccinia virus immunomodulators. Vaccine 34, 4827-34.

Stuart, J.H., Sumner, R.P., Lu, Y., Snowden, J.S. & Smith, G.L. (2016). Vaccinia virus protein C6 inhibits type I IFN signaling in the nucleus and binds to the transactivation domain of STAT2. PLoS Pathogens. 12, e1005955.

Duggan, A.T., Perdomo, M.F., Piombino-Mascali, D., Marciniak, S., Poinar, D., Jankauskas, R., Humphreys, M., Golding, B., Southon, J., Devault, A., Rouillard, J-M., Sahl, J.W., Dutour, O., Hedman, K., Sajantila, A., Smith, G.L., Holmes, E.C. & Poinar, H. (2016). 17th century variola virus reveals the recent history of smallpox. Current Biology, 26, 3407-3412.

Gao, W.N.D., Carpentier, D.C.J., Ewles, H.A., Lee, S.-A. & Smith, G.L. (2017). Vaccinia virus proteins A36 and F12/E2 show strong preferences for different kinesin light chain isoforms. Traffic 18, 505-18.