Pathogenesis and immunity to viral infections
I have a long term interest in the immune response to persistent viral infections. Presently we are studying the pathogenesis of gastrointestinal viruses using murine norovirus as a model virus. This can establish both acute and persistent infections. It may also spread from the gut to cause a systemic infection that can lead to pathology in different organ systems. As such it is both a good model system for studying gastrointestinal immunity and mechanisms of viral persistence. We are investigating the role of different cell types and factors in the gut that protect from infection as well as properties of the virus itself that affect its pathogenesis.
Previously I have worked with visnamaedi virus, a lentiviral infection of sheep. This is a model lentiviral infection with a strict tropism for macrophages and dendritic cells and as such allows the study of viral control mechanisms in the absence of immune deficiencies as is seen with HIV.
A common theme of my work is infection of dendritic cells and macrophages and how these infections alter the biology of these important immune cell types. This includes studies with Salmonella enterica as well as the virus infections above.
We designed and run the newest, state of the art biological Containment Level 3 (CL3) laboratory at the University as well as operate a new multiparamenter Flow sorting facility for single cell sorting of infectious samples under CL3 conditions. This new facility enables the isolation and direct sequencing of single cells of different types infected with a variety of different viral agents or transforming plasmids. We have made both our CL3 facilities and FACS CL3 Suite available for use by members of the University.
Salmonella enterica serovar Typhimurium trxA mutants are protective against virulent challenge, but induce less inflammation than the live-attenuated vaccine strain SL3261. Peters, S. E., Paterson, G. K., Bandularatne, E. S. D., Northen, H. C., Pleasance, S., Willers, C., Wang, J., Foote, A. K., Constantino-Casas, F., Scase, T. J., Blacklaws, B. A., Bryant, C. E., Mastroeni, P., Charles, I. G. & Maskell, D. J. (2010) Infect. Immun. 78, 326-336.
Molecular characterization of poxviruses associated with tattoo skin lesions in UK cetaceans. Blacklaws, B.A., Gajda, A. M., Tippelt, S., Jepson, P. D., Deaville, R., Van Bressem, M.-F., Pearce, G. P. (2013) PLOS ONE, 8, e71734.
Pathology caused by persistent murine norovirus infection. Shortland, A., Chettle, J., Archer, J., Wood, K., Bailey, D., Goodfellow, I., Blacklaws, B.A. & Heeney, J.L. (2014) J. Gen. Virol., 95, 413–422.
Differential expression of Toll-like receptors and inflammatory cytokines in ovine interdigital dermatitis and footrot. Davenport, R., Heawood, C., Sessford, K., Baker, M., Baiker, K., Blacklaws, B., Kaler, J., Green, L. & Tötemeyer, S. (2014) Vet. Immunol. Immunopathol. 161, 90-8.
Intestinal intraepithelial lymphocyte activation promotes innate antiviral resistance. Swamy, M., Abeler-Dörner, L., Chettle, J., Mahlakõiv, T., Goubau, D., Chakravarty, P., Ramsay, G., Reis e Sousa, C., Staeheli, P., Blacklaws, B.A., Heeney, J.L. & Hayday, A.C. (2015) Nature Comm. 6, 7090. doi: 10.1038/ncomms8090. PMID: 25987506