1. Immunology of livestock, in particular cattle and sheep: Cell-mediated immunity; innate immunity and the biology of toll-like receptors; regulatory T cells; immunity to viruses and parasites. Current work includes a study of toll-like receptor (TLR) polymorphisms and function in cattle and sheep, in particular TLR2 and TLR5. TLRs are innate immune receptors that recognise relatively-conserved constituents of microbes and parasites and alert the immune system of the affected host. We have discovered novel variants of TLR5 in cattle and are seeking their function. TLR5 recognises bacterial flagellin. D. Haig has led an innate immunity consortium, sponsored by Pfizer, BBSRC and ERAD of the Scottish Executive, which consists of the IAH (Compton /Pirbright), Roslin Institute (Edinburgh University), Moredun Research Institute (Edinburgh) and the Royal Veterinary College (London). 2. Virology: Current interest in the diagnosis, pathogenesis and control of herpesvirus infections of livestock, in particular those causing malignant catarrhal fever (MCF) in cattle, bison and deer. Current work includes understanding the unique pathogenesis of MCF (a fatal lymphoproliferative disease involving multiple organs incapacitated by indiscriminately-cytotoxic infected T cells). In particular the role, if any, of regulatory T cells in preventing MCF is being studied in a rabbit and hamster model of the disease. We also have just completed a large BBSRC-funded grant to improve our vaccine for MCF and implement field trials in cattle in Tanzania (see below). This vaccine has been eagerly awaited by pastoralists and farmers in eastern and southern Africa and has the potential, if successful to alter the ecology of the plains in this area, such is the importance of this disease. 3. Vaccine development: the use of toll-like receptor agonists as new generation adjuvants to improve existing vaccines and develop new ones. Initial work used particular TLR agonists (microbial products) to improve the longevity and efficacy of the vaccine against MCF caused by alcelaphine herpesvirus-1 (AlHV-1). D. Haig is the principal investigator of this BBSRC grant that also involves the University of Glasgow, Moredun Research Institute (Edinburgh) and Sokoine University of Agriculture and wildlife agencies in Tanzania. SOME RECENT REFERENCES:
1. C. J. McInnes, D. Deane, D. Haig, A. Percival, J. Thomson, and A. R. Wood (2005). Glycosylation, Disulfide bond formation, and the Presence of a WSXWS-like Motif in the Orf Virus GIF Protein Are Critical for Maintaining the Integrity of Binding to Ovine Granulocyte-Macrophage Colony-Stimulating Factor and interleukin-2. Journal of Virology 79: 11205-11213.
2. Fraser S, Nettleton P, Dutia B, Haig D and Russell G (2006). Development of an enzyme-linked immunosorbent assay for the detection of antibodies against malignant catarrhal fever viruses in cattle serum. Veterinary Microbiology 116: 21-28. 3. Thonur L, Russell G, Stewart J and Haig D (2006). Differential transcription of ovine herpesvirus-2 genes in lymphocytes from reservoir and susceptible species. Virus Genes 32: 27-35. 4. Dewals B, Boudry C, Gillet L, Markine-Goriaynoff N, de Leval L, Haig DM and Vanderplasschen A. (2006). Cloning of the genome of Alcelaphine herpesvirus 1 as an infectious and pathogenic bacterial artificial chromosome. Journal of General Virology 87: 509-517. 5. Hart J, Ackermann M, Jawardane G, Russell, G, Haig D, Reid H and Stewart J. (2007). Complete sequence and analysis of the ovine herpesvirus-2 genome. Journal of General Virology 88: 28-39. 6. Fleming SB, Anderson IE, Thomson J, Deane DL, McInnes CJ, McCaughan CA, Mercer AA, Haig DM. (2007). Infection with recombinant orf viruses demonstrates that the viral interleukin-10 is a virulence factor. Journal of General Virology 88: 1922-1927. 7. Anderson IE, Buxton D, Campbell I, Russell G, Davis WC, Hamilton MJ, Haig DM (2007). Immunohistochemical study of experimental malignant catarrhal fever in rabbits. Journal of Comparative Pathology 136: 156-166. 8. Hart J, Ackermann M, Jayawardane G, Russell G, Haig DM, Reid H, Stewart JP (2007). Complete sequence and analysis of the ovine herpesvirus 2 genome. Journal of General Virology 88:28-39. 9. Boudry, C., Markine-Goriaynoff, N., Delforge, C., Springael, J-Y., de Leval, L., Drion, P., Russell. G., Haig, D.M., Vanderplasschen, A. and Dewals, B (2007). The A5 gene of alcelaphine virus-1 encodes a constitutively-activated G-protein-coupled receptor that is non-essential for the induction of malignant catarrhal fever in rabbits. Journal of General Virology 88: 3224 - 3233. 10. Anderson, I., Deane, D., Swa, S., Thomson, J., Campbell, I., Buxton, D., Wei, X-Q., Stewart, J., Russell, G. and Haig, D.M (2008). Production and utilisation of interleukin-15 in malignant catarrhal fever. Journal of Comparative pathology 138:131-144. 11. Dry, I., Haig, D.M., Inglis, N.F., Imrie, L., Stewart, J.P., Russell, G.C. (2008) Proteomic analysis of pathogenic and attenuated Alcelaphine herpesvirus-1. Journal of Virology 82: 5390-5397. 12. Haig, D.M., Grant, D., Deane, D.L., Campbell, I., Thomson, J., Jepson, C., Buxton, D. and Russell, G.C. (2008). An immunisation strategy for the protection of cattle against alcelaphine herpesvirus-1-induced malignant catarrhal fever. Vaccine, 26: 4461-4468. 13. Jayawardane, G., Russell, G.C., Thomson, J., Deane, D.L., Cox, H, Ackermann, M., Haig, D.M. and Stewart, J.P (2008). A Captured Viral IL-10 with Cellular Exon Structure: Implications for Viral Evolution. Journal of General Virology, 89: 2447-2455. 14. Jann, O., Werling, D., Chang, J-S., Haig, D.M. and Glass, E.J. (2008). Molecular evolution of bovine TLR2 suggests substitutions of functional relevance. BMC Evol Biol 8:288-296. 15. Meier-Trummer CS, Tobler K, Hilbe M, Stewart JP, Hart J, Campbell I, Haig DM, Glauser DL, Ehrensperger F, Ackermann M. (2009). Ovine herpesvirus 2 structural proteins in epithelial cells and M-cells of the appendix in rabbits with malignant catarrhal fever. Veterinary Microbiology. 137:235-42. 16. Chang, J.S. , Russell, G.C., Jann, O., Glass, E.J., Werling, D. and Haig, D.M. (2009). Molecular cloning and characterization of toll-like receptors 1-10 in sheep. Veterinary Immunology and Immunopathology 127:94-105. 17. Kwong LS, Parsons R, Patterson R, Coffey TJ, Thonur L, Chang J, Russell G, Haig D, Werling D and Hope JC, 2011. Characterisation of antibodies to bovine Toll-Like Receptor (TLR)-2 And cross-reactivity with ovine TLR2. Veterinary Immunology And Immunopathology. 139(2-4), 313-8
2. Russell GC, Benavides J, Grant DM, Todd H, Thomson J, Puri V, Nath M, Haig DM. 2012. Host gene expression changes in cattle infected with Alcelaphine herpesvirus 1.Virus Res. 2012 Oct;169(1):246-54. doi: 10.1016/j.virusres.2012.08.011.
3. Smith SA, Jann OC, Haig D, Russell GC, Werling D, Glass EJ, Emes RD. 2012. Adaptive evolution of Toll-like receptor 5 in domesticated mammals. BMC Evol Biol. 2012 Jul 24;12:122. doi: 10.1186/1471-2148-12-122.
4. Russell GC, Benavides J, Grant D, Todd H, Deane D, Percival A, Thomson J, Connelly M, Haig DM. 2012. Duration of protective immunity and antibody responses in cattle immunised against alcelaphine herpesvirus-1-induced malignant catarrhal fever. Vet Res. 2012 Jun 11;43(1):51. doi: 10.1186/1297-9716-43-51.
5. Thonur L, Haig DM, Thomson J, Russell GC.2012. Toll-like receptor gene expression in fresh and archived ovine pseudoafferent lymph DEC205+ dendritic cells. J Comp Pathol. 2012 Aug-Oct;147(2-3):296-304. doi: 10.1016/j.jcpa.2012.01.005.
6. Russell, G. C., Todd, H., Deane, D., Percival, A., Dagleish, M. P., Haig, D. M., & Stewart, J. P. (2013). A novel spliced gene in alcelaphine herpesvirus 1 encodes a glycoprotein which is secreted in vitro. Journal of General Virology,94(Pt 11), 2515-2523.
7. Smith SA, Haig D, Emes RD. (2014). Novel ovine polymorphisms and adaptive evolution in mammalian TLR2 suggest existence of multiple pathogen binding regions. Gene. 2014 Feb 26. pii: S0378-1119(14)00221-2. doi: 10.1016/j.gene.2014.02.032. [Epub ahead of print]
8. Russell, G.C., Scholes S.F., Twomey, D.F., Courtenay, A.E., Grant, D.M., Lamond, B., Norris, D., Willoughby, K., Haig, D.M., Stewart, J.P. (2014). Analysis of the genetic diversity of ovine herpesvirus 2 in samples from livestock with malignant catarrhal fever. Vet. Microbiol., http://dx.doi.org/10.1016/j.vetmic.2014.04.011
9. Parameswaran, N., Dewals, B. G., Giles, T. C., Deppmann, C., Blythe, M., Vanderplasschen, A., & Haig, D. (2014). The A2 gene of alcelaphine herpesvirus-1 is a transcriptional regulator affecting cytotoxicity in virus-infected T cells but is not required for malignant catarrhal fever induction in rabbits. Virus research, 188, 68-80.
10. Parameswaran, N., Russell, G. C., Bartley, K., Grant, D. M., Deane, D., Todd, H., & Haig, D. M. (2014). The effect of the TLR9 ligand CpG-oligodeoxynucleotide on the protective immune response to alcelaphine herpesvirus-1-mediated malignant catarrhal fever in cattle. Veterinary Research, 45(1), 59.
11. Bartley, K., Deane, D., Percival, A., Dry, I. R., Grant, D. M., Inglis, N. F., ... & Russell, G. C. (2014). Identification of immuno-reactive capsid proteins of malignant catarrhal fever viruses. Veterinary microbiology, 173(1), 17-26.
12. Alkurashi, M. M., May, S. T., Kong, K., Bacardit, J., Haig, D., & Elsheikha, H. M. (2014). Susceptibility to experimental infection of the invertebrate locusts (Schistocerca gregaria) with the apicomplexan parasite Neospora caninum.PeerJ, 2, e674.
Poxvirus pathogenesis and control in livestock.
Immunity to nematodes in livestock and rodents.
The role of mast cells in allergy and infectious disease.
The in vivo dynamics of immune responses around regional lymph nodes using lymphatic cannulation.
The role of regulatory T cells in the pathogenesis of malignant catarrhal fever.
Vaccine strategy using new-generation adjuvants. Improvement of the vaccine for AlHV-1 MCF.
Pathogenesis and host-pathogen interactions in bovine respiratory disease.