David Haig

Contact

• workRoom B19 SVMS
  Sutton Bonington Campus
  Sutton Bonington
  Leicestershire
  LE12 5RD
  UK
• work0115 951 6450
• fax0115 951 6415
• david.haig@nottingham.ac.uk

Biography

Expertise in studying the immune response in livestock, particularly cattle and sheep; cell-mediated immunity has been studied in detail and this involved identification of T cell subsets and the cloning and characterisation of cytokines /lymphokines; lymphatic cannulation to study the in vivo dynamics of immune and inflammatory responses around single lymph nodes in response to helminth parasite or virus infections; The virology, pathogenesis and control of orf virus infection in sheep (a skin-tropic poxvirus causing orf / pustular dermatitis in sheep) and of herpesvirus infection of cattle causing malignant catarrhal fever (MCF); Immune responses and disease pathogenesis in mice, rats, rabbits and hamsters that provide laboratory animal models for viral diseases of interest; Expertise in the cloning, characterisation and biology of toll-like receptors (TLR) in sheep (and cattle along with collaborators) and characterisation of polymorphic variants of TLR2 and TLR5; Expertise in developing vaccines, most recently one against MCF that is undergoing field trials in Africa; Expertise in proteomics.

Expertise Summary

I have expertise in studying the immune response in livestock, particularly cattle and sheep. This expertise has been called on for various consultancies to Industy and Law firms over the years. Cell-mediated immunity has been studied in detail and this involved identification of T cell subsets and the cloning and characterisation of cytokines /lymphokines. I have used the lymphatic cannulation technique in sheep to study the in vivo dynamics of immune and inflammatory responses around single lymph nodes in response to helminth parasite or virus infections. I have studied the virology, pathogenesis and control of orf virus infection in sheep (a skin-tropic poxvirus causing orf / pustular dermatitis in sheep). I have also studied and continue to study the diagnosis, pathogenesis and control of herpesvirus infection of cattle causing malignant catarrhal fever (MCF). I have expertise in studying immune responses and disease pathogenesis in mice, rats, rabbits and hamsters that provide laboratory animal models for viral diseases of interest. I have expertise in the cloning, characterisation and biology of toll-like receptors (TLR) in sheep (and cattle along with collaborators) and characterisation of polymorphic variants of TLR2 and TLR5. TLRs are innate immune receptors involved in the recognition of microbes within the body. I have expertise in developing vaccines, most recently one against MCF that is undergoing field trials in Africa. I have experience and expertise in proteomics, having helped in the setting up of a proteomic unit at the Moredun Research Institute in Edinburgh.

Teaching Summary

Immunology and Virology

Research Summary

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.… read more

Selected Publications

• HAIG, DAVID M, GRANT, DAWN, DEANE, DAVID, CAMPBELL, IRIS, THOMSON, JACKIE, JEPSON, CATHERINE, BUXTON, DAVID and RUSSELL, GEORGE C, 2008. An immunisation strategy for the protection of cattle against alcelaphine herpesvirus-1-induced malignant catarrhal fever. Vaccine. 26(35), 4461-8
• DRY, INGA, HAIG, DAVID M, INGLIS, NEIL F, IMRIE, LISA, STEWART, JAMES P and RUSSELL, GEORGE C, 2008. Proteomic analysis of pathogenic and attenuated alcelaphine herpesvirus 1. Journal of virology. 82(11), 5390-7
• HART, JANE, ACKERMANN, MATHIAS, JAYAWARDANE, GAMINI, RUSSELL, GEORGE, HAIG, DAVID M, REID, HUGH and STEWART, JAMES P, 2007. Complete sequence and analysis of the ovine herpesvirus 2 genome. Journal of General Virology. 88(Pt 1), 28-39
• BOUDRY, C, MARKINE-GORIAYNOFF, N, DELFORGE, C, SPRINGAEL, J-Y, DE LEVAL, L, DRION, P, RUSSELL, G, HAIG, D M, VANDERPLASSCHEN, A F and DEWALS, B, 2007. The A5 gene of alcelaphine herpesvirus 1 encodes a constitutively active G-protein-coupled receptor that is non-essential for the induction of malignant catarrhal fever in rabbits. Journal of General Virology. 88(Pt 12), 3224-33

• View all publications

Current Research

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 currently leads 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 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 will use 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 a 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.

Past Research

Poxvirus pathogenesis and control in livestock.

Immunity to nematodes in livestock and rodents.

The role of mast cells in allergy and infectious disease.

Future Research

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.

• SMITH, S.A., JANN, O.C., HAIG, D., RUSSELL, G.C., WERLING, D., GLASS, E.J. and EMES, R.D., 2012. Adaptive evolution of toll-like receptor 5 in domesticated mammals BMC Evolutionary Biology. 12, 122
• RUSSELL GC, BENAVIDES J, GRANT D, TODD H, DEANE D, PERCIVAL A, THOMSON J, CONNELLY M and HAIG DM, 2012. Duration of protective immunity and antibody responses in cattle immunised against alcelaphine herpesvirus-1-induced malignant catarrhal fever. Veterinary research. 43(1), 51 (In Press.)
• THONUR L, HAIG DM, THOMSON J and RUSSELL GC, 2012. Toll-like receptor gene expression in fresh and archived ovine pseudoafferent lymph dec205(+) dendritic cells. Journal of comparative pathology. 147(2-3), 296-304
• GEORGE C. RUSSELL, JULIO BENAVIDES, DAWN GRANT, HELEN TODD, JACKIE THOMSON, VIPUL PURI, MINTU NATH AND DAVID M. HAIG., 2012. Host gene expression changes in cattle infected with Alcelaphine herpesvirus 1 Virus Research. (In Press.)
• 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
• MEIER-TRUMMER, CLAUDIA S, TOBLER, KURT, HILBE, MONIKA, STEWART, JAMES P, HART, JANE, CAMPBELL, IRIS, HAIG, DAVID M, GLAUSER, DANIEL L, EHRENSPERGER, FELIX and ACKERMANN, MATHIAS, 2009. Ovine herpesvirus 2 structural proteins in epithelial cells and M-cells of the appendix in rabbits with malignant catarrhal fever. Veterinary microbiology. 137(3-4), 235-42
• RUSSELL, GEORGE C, STEWART, JAMES P and HAIG, DAVID M, 2009. Malignant catarrhal fever: a review. Veterinary journal (London, England : 1997). 179(3), 324-35
• 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(1-2), 94-105
• ANDERSON, I E, BUXTON, D, CAMPBELL, I, RUSSELL, G, DAVIS, W C, HAMILTON, M J and HAIG, D M, 2008. Immunohistochemical study of experimental malignant catarrhal fever in rabbits. Journal of Comparative Pathology. 136(2-3), 156-66
• DRY, INGA, HAIG, DAVID M, INGLIS, NEIL F, IMRIE, LISA, STEWART, JAMES P and RUSSELL, GEORGE C, 2008. Proteomic analysis of pathogenic and attenuated alcelaphine herpesvirus 1. Journal of virology. 82(11), 5390-7
• JAYAWARDANE, G., RUSSELL, G.C., THOMSON, J., DEANE, D., COX, H., GATHERER, D., ACKERMANN, M., HAIG, D.M. and STEWART, J.P., 2008. A captured viral interleukin 10 gene with cellular exon structure. The Journal of General Virology: JGV. 89(10), 2447-55
• ANDERSON, I E, DEANE, D, SWA, S, THOMSON, J, CAMPBELL, I, BUXTON, D, WEI, X-Q, STEWART, J, RUSSELL, G and HAIG, D M, 2008. Production and utilization of interleukin-15 in malignant catarrhal fever. Journal of comparative pathology. 138(2-3), 131-44
• HAIG, DAVID M, GRANT, DAWN, DEANE, DAVID, CAMPBELL, IRIS, THOMSON, JACKIE, JEPSON, CATHERINE, BUXTON, DAVID and RUSSELL, GEORGE C, 2008. An immunisation strategy for the protection of cattle against alcelaphine herpesvirus-1-induced malignant catarrhal fever. Vaccine. 26(35), 4461-8
• JANN, O.C., WERLING, D., CHANG, J.-S., HAIG, D. and GLASS, E.J., 2008. Molecular evolution of bovine Toll-like receptor 2 suggests substitutions of functional relevance BMC Evolutionary Biology. 8, 288
• FLEMING, S.B., ANDERSON, I.E., THOMSON, J., DEANE, D.L., MCINNES, C.J., MCCAUGHAN, C.A., MERCER, A.A. and HAIG, D.M., 2007. Infection with recombinant orf viruses demonstrates that the viral interleukin-10 is a virulence factor Journal of General Virology. 88(7), 1922-1927
• HART, JANE, ACKERMANN, MATHIAS, JAYAWARDANE, GAMINI, RUSSELL, GEORGE, HAIG, DAVID M, REID, HUGH and STEWART, JAMES P, 2007. Complete sequence and analysis of the ovine herpesvirus 2 genome. Journal of General Virology. 88(Pt 1), 28-39
• BOUDRY, C, MARKINE-GORIAYNOFF, N, DELFORGE, C, SPRINGAEL, J-Y, DE LEVAL, L, DRION, P, RUSSELL, G, HAIG, D M, VANDERPLASSCHEN, A F and DEWALS, B, 2007. The A5 gene of alcelaphine herpesvirus 1 encodes a constitutively active G-protein-coupled receptor that is non-essential for the induction of malignant catarrhal fever in rabbits. Journal of General Virology. 88(Pt 12), 3224-33
• THONUR, L., RUSSELL, G.C., STEWART, J.P. and HAIG, D.M., 2006. Differential transcription of ovine herpesvirus 2 genes in lymphocytes from reservoir and susceptible species Virus Genes. 32(1), 27-35
• DEWALS, B, BOUDRY, C, GILLET, L, MARKINE-GORIAYNOFF, N, DE LEVAL, L, HAIG, D M 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(Pt 3), 509-17
• FRASER, S J, NETTLETON, P F, DUTIA, B M, HAIG, D M and RUSSELL, G C, 2006. Development of an enzyme-linked immunosorbent assay for the detection of antibodies against malignant catarrhal fever viruses in cattle serum. Veterinary Microbiology. 116(1-3), 21-8
• HAIG, DAVID M, 2006. Orf virus infection and host immunity. Current Opinion in Infectious Diseases. 19(2), 127-31
• MCINNES, C J, DEANE, D, HAIG, D, PERCIVAL, A, THOMSON, J and WOOD, A R, 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(17), 11205-13
• LI, HONG, GAILBREATH, KATHERINE, FLACH, EDMUND J, TAUS, NAOMI S, COOLEY, JIM, KELLER, JANICE, RUSSELL, GEORGE C, KNOWLES, DONALD P, HAIG, DAVID M, OAKS, J LINDSAY, TRAUL, DONALD L and CRAWFORD, TIMOTHY B, 2005. A novel subgroup of rhadinoviruses in ruminants. Journal of General Virology. 86(Pt 11), 3021-6
• WRIGHT, H, STEWART, J P, IRERI, R G, CAMPBELL, I, POW, I, REID, H W and HAIG, D M, 2003. Genome re-arrangements associated with loss of pathogenicity of the gamma-herpesvirus alcelaphine herpesvirus-1. Research in Veterinary Science. 75(2), 163-8
• HAIG, D.M., THOMSON, J., MCINNES, C.J., DEANE, D.L., ANDERSON, I.E., MCCAUGHAN, C.A., IMLACH, W., MERCER, A.A., HOWARD, C.J. and FLEMING, S.B., 2002. A comparison of the anti-inflammatory and immuno-stimulatory activities of orf virus and ovine interleukin-10 Virus Research. 90(1-2), 303-316
• HAIG, DAVID M, THOMSON, JACKIE, MCINNES, COLIN, MCCAUGHAN, CATHERINE, IMLACH, WENDY, MERCER, ANDREW and FLEMING, STEPHEN, 2002. Orf virus immuno-modulation and the host immune response. Veterinary Immunology and Immunopathology. 87(3-4), 395-9
• IMLACH, WENDY, MCCAUGHAN, CATHERINE A, MERCER, ANDREW A, HAIG, DAVID and FLEMING, STEPHEN B, 2002. Orf virus-encoded interleukin-10 stimulates the proliferation of murine mast cells and inhibits cytokine synthesis in murine peritoneal macrophages. Journal of General Virology. 83(Pt 5), 1049-58
• HAIG, DAVID M and MCINNES, COLIN J, 2002. Immunity and counter-immunity during infection with the parapoxvirus orf virus. Virus research. 88(1-2), 3-16
• SWA, S., WRIGHT, H., THOMSON, J., REID, H. and HAIG, D., 2001. Constitutive activation of Lck and Fyn tyrosine kinases in large granular lymphocytes infected with the γ-herpesvirus agents of malignant catarrhal fever Immunology. 102(1), 44-52
• ANDERSON, I E, REID, H W, NETTLETON, P F, MCINNES, C J and HAIG, D M, 2001. Detection of cellular cytokine mRNA expression during orf virus infection in sheep: differential interferon-gamma mRNA expression by cells in primary versus reinfection skin lesions. Veterinary Immunology and Immunopathology. 83(3-4), 161-76
• HAIG, D M, 2001. Subversion and piracy: DNA viruses and immune evasion. Research in Veterinary Science. 70(3), 205-19
• FLEMING, S B, HAIG, D M, NETTLETON, P, REID, H W, MCCAUGHAN, C A, WISE, L M and MERCER, A, 2000. Sequence and functional analysis of a homolog of interleukin-10 encoded by the parapoxvirus orf virus. Virus genes. 21(1-2), 85-95
• LLOYD, J B, GILL, H S, HAIG, D M and HUSBAND, A J, 2000. In vivo T-cell subset depletion suggests that CD4+ T-cells and a humoral immune response are important for the elimination of orf virus from the skin of sheep. Veterinary immunology and immunopathology. 74(3-4), 249-62
• DEANE, D, MCINNES, C J, PERCIVAL, A, WOOD, A, THOMSON, J, LEAR, A, GILRAY, J, FLEMING, S, MERCER, A and HAIG, D, 2000. Orf virus encodes a novel secreted protein inhibitor of granulocyte-macrophage colony-stimulating factor and interleukin-2. Journal of virology. 74(3), 1313-20