Applied and molecular immunology, viral pathogenesis and molecular virology
Virus host interactions, in particular accessory factors that parapoxviruses encode to subvert host defence mechanisms and to modify cell physiological processes.
Orf virus is a large DNA poxvirus and is the type species of the parapoxvirus genus of the family poxviridae. It causes pustular dermatitis in sheep and goats and is transmissible to humans. An interesting feature of this virus is that it has evolved a unique set of virulence factors that allows it to subvert the host immune responses and to modify host physiological processes. These factors may explain why this virus is able to reinfect its host. We and others have discovered genes such as a homologue of interleukin-10, a vascular endothelial growth factors, a factor that binds granulocyte macrophage colony stimulating factor and IL-2 and a chemokine binding protein. In addition we have discovered factors that block apoptosis and the interferon response and have identified a number of genes in orf virus for which functions are not known. Projects are offered to further characterise the function of the parapoxvirus accessory factors and to identify and characterise the function of unknown genes.
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.
Fleming S.B. and Mercer AA. Orf virus. In Molecular detection of Viral Pathogens. Editor Don Liu. Publisher Taylor and Francis, Boca Raton, Florida. In press.
Z. Lateef, MA Baird, LM Wise, S Young, AA Mercer and SB Fleming. (2010). The chemokine-binding protein encoded by the poxvirus orf virus inhibits recruitment of dendritic cells to sites of skin inflammation and migration to peripheral lymph nodes. Cellular Microbiology 12 (5) 665-676.
Mo Min, SB Fleming, AA Mercer (2010). Changing pace: viral mimicry of an anaphase promoting complex subunit. Cell Cycle 6(4) 632-3.
Mo Min, SB Fleming, AA Mercer (2009). Cell cycle deregulation by a poxvirus partial mimic of the anaphase promoting complex subunit 11. PNAS.106(46) 19527-32.
D. Westphal, EC Ledgerwood, JD Tyndall, MH Hibma, N Ueda, SB Fleming and AA Mercer. (2009). The orf virus inhibitor of apoptosis functions in a Bcl-2-like manner binding and neutralizing a set of BH3 only proteins and active Bax. Apoptosis 14(11) 1317-30
A.H.N. Erickson, A. Wise, S. Fleming, A Molinaro, M. Teboh-Ewungkem, M. Baird, Z. Lateef, L. De Pillis. (2009). A preliminary mathematical model of skin dendritic cell trafficking and induction of T cell immunity. AIMS Journals. Discrete and Continuous Dynamical Systems Series B. Vol 12, No 2, p. 323- 326
Z. Lateef, M.A. Baird, L.M. Wise, A.A. Mercer, S.B. Fleming. (2009). Orf virus-encoded chemokine binding protein is a potent inhibitor of monocyte recruitment in a mouse skin model. J. Gen. Virol. 90, 1477-82
D. Deane, N. Ueda, L.M. Wise, A.R. Wood, A. Percival, C. Jepson, N.F. Inglis, S.B. Fleming, A.A. Mercer, C.J. Innes. (2009). Conservation and Variation of the parapoxvirus GM-CSF-inhibitory factor (GIF) proteins. J. Gen. Virol. 90, 970-977.
JL. Tan, N. Ueda, A.A. Mercer and S.B. Fleming. (2009). Investigation of orf virus structure and morphogenesis using recombinants expressing FLAG-tagged envelope structural proteins: evidence for wrapped virus particles and egress from infected cells. J. Gen. Virol. 90, 614-625.
S. Sonnberg, SB Fleming, AA Mercer. (2009). A truncated two-a-helix F-box present in poxvirus ankyrin-repeat proteins is sufficient for binding to SCF1 ubiquitin ligase complex. J.Gen. Virol 90, 1224-1228.
S. Sonnberg, B.T. Seet, T. Pawson, S.B. Fleming, A.A. Mercer. (2008). Poxvirus ankyrin repeat proteins are a unique class of F-box proteins that associate with cellular SCF1 ubiquitin ligase complexes. PNAS. 105, 10955-10960.
MK Inder, LM Wise, SB Fleming, AA Mercer. 2008. The C-terminus of viral vascular endothelial growth factor-E partially blocks binding to VEGF receptor-1. FEBS J. 275, 207-217
D. Westphal, E.C. Ledgerwood, M.H. Hibma, S.B. Fleming, E.M. Whelan, A.A. Mercer. 2007. A novel Bcl-2-like inhibitor of apoptosis is encoded by the parapoxvirus, orf virus. J.Virology, 81, 7178-7188
L.M. Wise, L.J. Savory, N.H. Dryden, E.M. Whelan S.B. Fleming, A.A. Mercer. 2007. Major amino acid sequence variants of viral vascular endothelial growth factor are functionally equivalent during Orf virus infection of sheep skin. Virus Research, 128, 115-125
S.B Fleming, I.E. Anderson, J Thomson, D.L. Deane, C.J. McInnes, C.A. McCaughan, A.A. Mercer and D.M. Haig. 2007. Infection with recombinant orf viruses demonstrates that viral interleukin-10 is a virulence factor. J. Gen Virol 88, 1922-1927
L.Wise, C McCaughan, CK Tan, AA Mercer, SB Fleming. 2007. Orf virus IL-10 inhibits cytokine synthesis in human THP-1 monocytes but only partially impairs their proliferation. J. Gen Virol 88, 1677-1682
M.K. Inder, N. Ueda, A.A. Mercer, S.B. Fleming, L.M. Wise. 2007. Bovine papular stomatitis virus encodes a functionally distinct VEGF that binds VEGFR-1 and VEGFR-2. J. Gen. Virol. 88: 781-791.
A. Chan, M. Baird, A.A. Mercer, S.B. Fleming. 2006. Maturation and function of human dendritic cells are inhibited by orf virus-encoded interleukin-10. J. Gen. Virol 87, 3177-3181.
N. Ueda, M. Inder, L. M. Wise, S. B. Fleming, A.A. Mercer. 2007. Parapoxvirus of red deer in New Zealand encodes a variant of viral vascular endothelial growth factor. Virus Research 124, 50-8
A. A. Mercer, N. Ueda, S. M. Friederichs, K. Hofmann, K. M. Fraser, T Bateman, S. B. Fleming. 2005. Comparative analysis of genome sequences of three isolates of orf virus reveals unexpected sequence variation. Virus Research 116, 146-158.
A. A. Mercer, S. B. Fleming and N. Ueda. 2005 F-Box-like domains are present in most poxvirus ankyrin repeat proteins. Virus Genes 31, 127-133