Structural biology, vaccines, viral pathogenesis, molecular virology
Unraveling, combatting and exploiting new knowledge of viral virulence and pathogenicity.
Our Programme of work integrates 2 core themes: (1) combating viruses and (2) exploiting viruses for beneficial purposes,
Unraveling the complex interactions between viruses and humans reveals sophisticated viral replication strategies but, importantly, it also gives unique insights into our own physiology and immune defences. Furthermore, and rather paradoxically, viruses are proving to be an exciting source of new therapeutics for the treatment of a wide range of human diseases. The large complex poxvirus, orf virus, causes severe skin lesions that, remarkably, heal without scarring. Our studies have revealed that this virus expresses an astonishing array of novel proteins that may explain this phenomenon. Some of these viral proteins are secreted from infected cells and dampen inflammation or increase blood supply to infected tissue, while others work within infected cells to protect the virus from our defences. Our goal is to develop these orf viral proteins as new therapeutics for the treatment of acute and chronic human conditions including skin wounds, cancer, inflammatory disorders and chronic viral infection.The success of poxviruses such as orf virus is critically linked to their expression of multiple factors that manipulate host responses to infection. Orf virus encodes a unique repertoire of such factors. The potential for pathogen - encoded analogs of cellular factors to provide new therapeutics is now well recognised and our work is contributing to this growing field, with potential benefits to a wide range of human diseases and conditions.
Weber O, Mercer AA, Friebe A, Knolle P, Volk HD. 2013. Therapeutic Immunomodulation Using a Virus – The Potential of Inactivated orf virus. Eur J Clin Microbiol Infect Dis. 32(4):451-460.
Lyn M. Wise, Marie K. Inder, Nicola C. Real, Gabriella S. Stuart, Stephen B. Fleming and Andrew A. Mercer. 2012. The vascular endothelial growth factor encoded by orf virus regulates keratinocyte proliferation and migration and promotes epidermal regeneration. Cellular Microbiology, 14(9):1376-1390.
Min Mo, Saleha Shahar Stephen B Fleming, and Andrew A Mercer. 2012. How viruses affect the cell cycle through manipulation of APC/C. Trends in Microbiology, 20(9): 440-448.
Dutton S, Fleming SB, Ueda N, Heath DD, Hibma MH, Mercer AA (2012). Delivery of Echinococcus granulosus antigen EG95 to mice and sheep using recombinant vaccinia virus. Parasite Immunology 34(6):312-7.
Rintoul JL, Lemay CG, Tai LH, Stanford MM, Falls TJ, de Souza CT, Bridle BW, Daneshmand M, Ohashi PS, Wan Y, Lichty BD, Mercer AA, Auer RC, Atkins HL, Bell JC. 2012. ORFV: A Novel Oncolytic and Immune Stimulating Parapoxvirus Therapeutic. Mol Ther. 2012 20(6):1148-1157.
Stephanie Sonnberg, Stephen B. Fleming, and Andrew Mercer (2011). Phylogenetic analysis of the large family of poxvirus ankyrin-repeat proteins reveals ortholog groups within and across chordopoxvirus genera?. J. Gen. Virol. 92(11): p. 2596-2607.
Min Mo, Stephen B Fleming, and Andrew A Mercer. 2010. The Orf virus cell cycle regulator, PACR, competes with subunit 11 of the anaphase promoting complex for incorporation into the complex. Journal of General Virology 91: 3010-3015.
Min Mo, Stephen B Fleming, and Andrew A Mercer. 2009. Cell cycle deregulation by a poxvirus partial mimic of anaphase promoting complex subunit 11. Proc. Nat. Acad. Sci. (USA) 106(46): 19527-19532.
Stephanie Sonnberg, Bruce T. Seet, Tony Pawson, Stephen B. Fleming and Andrew A. Mercer. 2008. Poxvirus ankyrin repeat proteins are a unique class of F-box proteins that associate with cellular SCF1 ubiquitin ligase complexes. Proc. Nat. Acad. Sci. (USA) 105(31): 10955-10960.
Marie Inder, Lyn Wise, Stephen Fleming, and Andrew Mercer. 2008. The C-terminus of viral vascular endothelial growth factor (VEGF) partially blocks binding to VEGF receptor-1. FEBS Journal, FEBS J. 275(1): 207-217.
Dana Westphal, Elizabeth C. Ledgerwood, Merilyn H. Hibma, Stephen B. Fleming, Ellena M. Whelan, and Andrew A. Mercer. 2007. A novel Bcl-2-like inhibitor of apoptosis is encoded by the parapoxvirus, Orf virus. J Virol 81(13): 7178-7188.
Fleming, S.B. and A.A. Mercer. 2007. Genus Parapoxvirus. In Poxviruses. A.A. Mercer, A. Schmidt and O.Weber, editors. In the series Birkhaeuser Advances in Infectious Diseases, Series editors A. Schmidt, M. Wolff and S. Kaufmann. Birkhaeuser Verlag, Basel. p. 127-165.
Andrew A. Mercer, Norihito Ueda, Sonja-Maria Friederichs, Kay Hofmann, Kate M. Fraser, Trudie Bateman and Stephen B. Fleming (2006). Comparative analysis of genome sequences of three isolates of Orf virus reveals unexpected sequence variation. Virus Research, 116(1-2): 146-158.
Andrew A Mercer, Stephen B Fleming and Norihito Ueda. (2005). F-box-like domains in poxvirus ankyrin repeat proteins. Virus Genes 31(2): 127-133.
Bruce T. Seet , Catherine A. McCaughan , Tracy M. Handel , Andrew Mercer, Craig Brunetti , Grant McFadden, and Stephen B. Fleming. (2003). Analysis of an orf virus chemokine-binding protein: Shifting ligand specificities among a family of poxvirus viroceptors. Proc. Nat. Acad. Sci. (USA) 100 (25): 15137-15142.
Lyn M. Wise, Norihito Ueda, Nicola H. Dryden, Stephen B. Fleming, Carol Caesar, Sally Roufail, Marc G. Achen Steven A. Stacker, and Andrew A. Mercer. (2003). Viral Vascular Endothelial Growth Factors Vary Extensively in Amino Acid Sequence, Receptor-binding Specificities, and the Ability to Induce Vascular Permeability yet are Uniformly Active Mitogens. J. Biol. Chem. 278: 38004-38014.