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Health Sciences profile

Dr Stephen Fleming

PositionSenior Research Fellow
DepartmentDepartment of Microbiology and Immunology
QualificationsBSc PhD (Otago)
Research summaryApplied and molecular immunology, viral pathogenesis and molecular virology

Research

Virus host interactions, in particular accessory factors that parapoxviruses encode to subvert host defence mechanisms and to modify cell physiological processes.

Publications

Lateef, Z., Stuart, G., Jones, N., Mercer, A., Fleming, S., & Wise, L. (2019). The cutaneous inflammatory response to thermal burn injury in a murine model. International Journal of Molecular Sciences, 20(3), 538. doi: 10.3390/ijms20030538

Wise, L. M., Stuart, G. S., Real, N. C., Fleming, S. B., & Mercer, A. A. (2018). VEGF receptor-2 activation mediated by VEGF-E limits scar tissue formation following cutaneous injury. Advances in Wound Care, 7(8), 283-297. doi: 10.1089/wound.2016.0721

Fleming, S. B., McCaughan, C., Lateef, Z., Dunn, A., Wise, L. M., Real, N. C., & Mercer, A. A. (2017). Deletion of the chemokine binding protein gene from the Parapoxvirus Orf virus reduces virulence and pathogenesis in sheep. Frontiers in Microbiology, 8, 46. doi: 10.3389/fmicb.2017.00046

Chen, D.-Y., Fabrizio, J.-A., Wilkins, S. E., Dave, K. A., Gorman, J. J., Gleadle, J. M., Fleming, S. B., … Mercer, A. A. (2017). Ankyrin repeat proteins of orf virus influence the cellular hypoxia response pathway. Journal of Virology, 91(1), e01430-16. doi: 10.1128/jvi.01430-16

Sharif, S., Nakatani, Y., Wise, L., Corbett, M., Real, N. C., Stuart, G. S., Lateef, Z., Krause, K., Mercer, A. A., & Fleming, S. B. (2016). A broad-spectrum chemokine-binding protein of bovine papular stomatitis virus inhibits neutrophil and monocyte infiltration in inflammatory and wound models of mouse skin. PLoS ONE, 11(12), e0168007. doi: 10.1371/journal.pone.0168007

Chapter in Book - Research

Mercer, A., & Fleming, S. (2012). Parapoxvirus: Poxviridae, Chordopoxvirinae. In C. Tidona & G. Darai (Eds.), The Springer Index of Viruses. (pp. 1495-1504). New York: Springer. doi: 10.1007/978-0-387-95919-1_244

Fleming, S. B., & Mercer, A. A. (2010). Orf virus. In D. Liu (Ed.), Molecular detection of human viral pathogens. (pp. 1017-1027). CRC Press.

Fleming, S. B., & Mercer, A. A. (2007). Genus Parapoxvirus. In A. A. Mercer, A. Schmidt & O. Weber (Eds.), Poxviruses. (pp. 127-166). Basel, Switzerland: Birkhäuser.

Mercer, A., & Fleming, S. (2002). Parapoxviruses. In Springer Index of Viruses. (pp. 896-901). Berlin: Springer Press.

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Journal - Research Article

Lateef, Z., Stuart, G., Jones, N., Mercer, A., Fleming, S., & Wise, L. (2019). The cutaneous inflammatory response to thermal burn injury in a murine model. International Journal of Molecular Sciences, 20(3), 538. doi: 10.3390/ijms20030538

Wise, L. M., Stuart, G. S., Real, N. C., Fleming, S. B., & Mercer, A. A. (2018). VEGF receptor-2 activation mediated by VEGF-E limits scar tissue formation following cutaneous injury. Advances in Wound Care, 7(8), 283-297. doi: 10.1089/wound.2016.0721

Fleming, S. B., McCaughan, C., Lateef, Z., Dunn, A., Wise, L. M., Real, N. C., & Mercer, A. A. (2017). Deletion of the chemokine binding protein gene from the Parapoxvirus Orf virus reduces virulence and pathogenesis in sheep. Frontiers in Microbiology, 8, 46. doi: 10.3389/fmicb.2017.00046

Chen, D.-Y., Fabrizio, J.-A., Wilkins, S. E., Dave, K. A., Gorman, J. J., Gleadle, J. M., Fleming, S. B., … Mercer, A. A. (2017). Ankyrin repeat proteins of orf virus influence the cellular hypoxia response pathway. Journal of Virology, 91(1), e01430-16. doi: 10.1128/jvi.01430-16

Sharif, S., Nakatani, Y., Wise, L., Corbett, M., Real, N. C., Stuart, G. S., Lateef, Z., Krause, K., Mercer, A. A., & Fleming, S. B. (2016). A broad-spectrum chemokine-binding protein of bovine papular stomatitis virus inhibits neutrophil and monocyte infiltration in inflammatory and wound models of mouse skin. PLoS ONE, 11(12), e0168007. doi: 10.1371/journal.pone.0168007

Bennett, J. R., Lateef, Z., Fleming, S. B., Mercer, A. A., & Wise, L. M. (2016). Orf virus IL-10 reduces monocyte, dendritic cell and mast cell recruitment to inflamed skin. Virus Research, 213, 230-237. doi: 10.1016/j.virusres.2015.12.015

Fleming, S. B. (2016). Viral inhibition of the IFN-induced JAK/STAT signalling pathway: Development of live attenuated vaccines by mutation of viral-encoded IFN-antagonists. Vaccines, 4(3), 23. doi: 10.3390/vaccines4030023

Fleming, S. B., Wise, L. M., & Mercer, A. A. (2015). Molecular genetic analysis of Orf virus: A poxvirus that has adapted to skin. Viruses, 7(3), 1505-1539. doi: 10.3390/v7031505

Lee, S., Chu, H. X., Kim, H. A., Real, N. C., Sharif, S., Fleming, S. B., Mercer, A. A., Wise, L. M., … Sobey, C. G. (2015). Effect of a broad-specificity chemokine-binding protein on brain leukocyte infiltration and infarct development. Stroke, 46, 537-544. doi: 10.1161/strokeaha.114.007298

Couñago, R. M., Knapp, K. M., Nakatani, Y., Fleming, S. B., Corbett, M., Wise, L. M., Mercer, A. A., & Krause, K. L. (2015). Structures of orf virus chemokine binding protein in complex with host chemokines reveal clues to broad binding specificity. Structure, 23(7), 1199-1213. doi: 10.1016/j.str.2015.04.023

Harvey, R., McCaughan, C., Wise, L. M., Mercer, A. A., & Fleming, S. B. (2015). Orf virus inhibits interferon stimulated gene expression and modulates the JAK/STAT signalling pathway. Virus Research, 208, 180-188. doi: 10.1016/j.virusres.2015.06.014

Fleming, S., Yannakou, C. K., Haeusler, G. M., Clark, J., Grigg, A., Heath, C. H., … Weinkove, R., & Slavin, M. A. (2014). Consensus guide for antifungal prophylaxis in haematological malignancy and haemopoietic stem cell transplantation, 2014. Internal Medicine Journal, 44, 1283-1297. doi: 10.1111/imj.12595

Wise, L. M., Stuart, G. S., Real, N. C., Fleming, S. B., & Mercer, A. A. (2014). Orf virus IL-10 accelerates wound healing while limiting inflammation and scarring. Wound Repair & Regeneration, 22(3), 356-367. doi: 10.1111/wrr.12169

Dutton, S., Fleming, S. B., Ueda, N., Heath, D. D., Hibma, M. H., & Mercer, A. A. (2012). Delivery of Echinococcus granulosus antigen EG95 to mice and sheep using recombinant vaccinia virus. Parasite Immunology, 34(6), 312-317. doi: 10.1111/j.1365-3024.2012.01360.x

Mo, M., Shahar, S., Fleming, S. B., & Mercer, A. A. (2012). How viruses affect the cell cycle through manipulation of the APC/C. Trends in Microbiology, 20(9), 440-448. doi: 10.1016/j.tim.2012.05.007

Tan, J. L., Ueda, N., Heath, D., Mercer, A. A., & Fleming, S. B. (2012). Development of orf virus as a bifunctional recombinant vaccine: Surface display of Echinococcus granulosus antigen EG95 by fusion to membrane structural proteins. Vaccine, 30(2), 398-406. doi: 10.1016/j.vaccine.2011.10.079

Wise, L. M., Inder, M. K., Real, N. C., Stuart, G. S., Fleming, S. B., & Mercer, A. A. (2012). The vascular endothelial growth factor (VEGF)-E encoded by orf virus regulates keratinocyte proliferation and migration and promotes epidermal regeneration. Cellular Microbiology, 14(9), 1376-1390. doi: 10.1111/j.1462-5822.2012.01802.x

Sonnberg, S., Fleming, S. B., & Mercer, A. A. (2011). Phylogenetic analysis of the large family of poxvirus ankyrin-repeat proteins reveals orthologue groups within and across chordopoxvirus genera. Journal of General Virology, 92(11), 2596-2607. doi: 10.1099/vir.0.033654-0

Cross, M. L., Fleming, S. B., Cowan, P. E., Scobie, S., Whelan, E., Prada, D., Mercer, A. A., & Duckworth, J. A. (2011). Vaccinia virus as a vaccine delivery system for marsupial wildlife. Vaccine, 29(28), 4537-4543. doi: 10.1016/j.vaccine.2011.04.093

Lateef, Z., Baird, M. A., Wise, L. M., Young, S., Mercer, A. A., & Fleming, S. B. (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. doi: 10.1111/j.1462-5822.2009.01425.x

Mo, M., Fleming, S. B., & Mercer, A. A. (2010). 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. doi: 10.1099/vir.0.026054-0

Couñago, R. M., Fleming, S. B., Mercer, A. A., & Krause, K. L. (2010). Crystallization and preliminary X-ray analysis of the chemokine-binding protein from orf virus (Poxviridae). Acta Crystallographica Section F, F66, 819-823. doi: 10.1107/S1744309110018166

Lateef, Z., Baird, M. A., Wise, L. M., Mercer, A. A., & Fleming, S. B. (2009). Orf virus-encoded chemokine-binding protein is a potent inhibitor of inflammatory monocyte recruitment in a mouse skin model. Journal of General Virology, 90(6), 1477-1482. doi: 10.1099/vir.0.009589-0

Erickson, A. H. L., Wise, A., Fleming, S., Baird, M., Lateef, Z., Molinaro, A., … de Pillis, L. (2009). A preliminary mathematical model of skin dendritic cell trafficking and induction of T cell imunity. Discrete & Continuous Dynamical Systems Series B, 12(2), 323-336. doi: 10.3934/dcdsb.2009.12.323

Deane, D., Ueda, N., Wise, L. M., Wood, A. R., Percival, A., Jepson, C., … Fleming, S. B., Mercer, A. A., & McInnes, C. J. (2009). Conservation and variation of the parapoxvirus GM-CSF-inhibitory factor (GIF) proteins. Journal of General Virology, 90, 970-977. doi: 10.1099/vir.0.006692-0

Sonnberg, S., Fleming, S. B., & Mercer, A. A. (2009). A truncated two-α-helix F-box present in poxvirus ankyrin-repeat proteins is sufficient for binding the SCF1 ubiquitin ligase complex. Journal of General Virology, 90, 1224-1228. doi: 10.1099/vir.0.009324-0

Westphal, D., Ledgerwood, E. C., Tyndall, J. D. A., Hibma, M. H., Ueda, N., Fleming, S. B., & Mercer, A. A. (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), 1317-1330. doi: 10.1007/s10495-009-0403-1

Tan, J. L., Ueda, N., Mercer, A. A., & Fleming, S. B. (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. Journal of General Virology, 90(3), 614-625. doi: 10.1099/vir.0.005488-0

Mo, M., Fleming, S. B., & Mercer, A. A. (2009). Cell cycle deregulation by a poxvirus partial mimic of anaphase-promoting complex subunit 11. PNAS, 106(46), 19527-19532. doi: 10.1073/pnas.0905893106

Inder, M. K., Wise, L. M., Fleming, S. B., & Mercer, A. A. (2008). The C-terminus of viral vascular endothelial growth factor-E partially blocks binding to VEGF receptor-1. FEBS Journal, 275(1), 207-217. doi: 10.1111/j.1742-4658.2007.06189.x

Sonnberg, S., Seet, B. T., Pawson, T., Fleming, S. B., & Mercer, A. A. (2008). Poxvirus ankyrin repeat proteins are a unique class of F-box proteins that associate with cellular SCF1 ubiquitin ligase complexes. PNAS, 105(31), 10955-10960. doi: 10.1073/pnas.0802042105

Wise, L., McCaughan, C., Tan, C. K., Mercer, A. A., & Fleming, S. B. (2007). Orf virus interleukin-10 inhibits cytokine synthesis in activated human THP-1 monocytes, but only partially impairs their proliferation. Journal of General Virology, 88, 1677-1682.

Wise, L. M., Savory, L. J., Dryden, N. H., Whelan, E. M., Fleming, S. B., & Mercer, A. A. (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.

Inder, M. K., Ueda, N., Mercer, A. A., Fleming, S. B., & Wise, L. M. (2007). Bovine papular stomatitis virus encodes a functionally distinct VEGF that binds both VEGFR-1 and VEGFR-2. Journal of General Virology, 88, 781-791.

Fleming, S. B., Anderson, I. E., Thomson, J., Deane, D. L., McInnes, C. J., McCaughan, C. A., Mercer, A. A., & Haig, D. M. (2007). Infection with recombinant orf viruses demonstrates that the viral interleukin-10 is a virulence factor. Journal of General Virology, 88, 1922-1927.

Westphal, D., Ledgerwood, E. C., Hibma, M. H., Fleming, S. B., Whelan, E. M., & Mercer, A. A. (2007). A novel Bcl-2-like inhibitor of apoptosis is encoded by the parapoxvirus orf virus. Journal of Virology, 81(13), 7178-7188.

Ueda, N., Inder, M. K., Wise, L. M., Fleming, S. B., & Mercer, A. A. (2007). Parapoxvirus of red deer in New Zealand encodes a variant of viral vascular endothelial growth factor. Virus Research, 124, 50-58.

Chan, A., Baird, M., Mercer, A. A., & Fleming, S. B. (2006). Maturation and function of human dendritic cells are inhibited by orf virus-encoded interleukin-10. Journal of General Virology, 87, 3177-3181.

Mercer, A. A., Ueda, N., Friederichs, S.-M., Hofmann, K., Fraser, K. M., Bateman, T., & Fleming, S. B. (2006). Comparative analysis of genome sequences of three isolates of Orf virus reveals unexpected sequence variation. Virus Research, 116, 146-158.

Mercer, A. A., Fleming, S. B., & Ueda, N. (2005). F-box-like domains are present in most poxvirus ankyrin repeat proteins. Virus Genes, 31(2), 127-133.

Wise, L., Ueda, N., Dryden, N. H., Fleming, S. B., Caesar, C., Roufail, S., … Mercer, A. A. (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. Journal of Biological Chemistry, 278(39), 38004-38014.

Seet, B. T., McCaughan, C. A., Handel, T. M., Mercer, A. A., Brunetti, C., McFadden, G., & Fleming, S. B. (2003). Analysis of an orf virus chemokine-binding protein: Shifting ligand specificities among a family of poxvirus viroceptors. PNAS, 100(25), 15137-15142.

Ueda, N., Wise, L., Stacker, S. A., Fleming, S. B., & Mercer, A. A. (2003). Pseudocowpox virus encodes a homolog of vascular endothelial growth factor. Virology, 305, 298-309.

Lateef, Z., Fleming, S. B., Halliday, G., Faulkner, L., Mercer, A. A., & Baird, M. A. (2003). Orf virus-encoded interleukin-10 inhibits maturation, antigen presentation and migration of murine dendritic cells. Journal of General Virology, 84, 1101-1109.

Haig, D. M., Thomson, J., McInnes, C. J., McCaughan, C. A., Imlach, W., Mercer, A. A., & Fleming, S. B. (2002). Orf virus immuno-modulation and the host immune response. Veterinary Immunology & Immunopathology, 87(3-4), 395-399.

Mercer, A. A., Wise, L. M., Scagliarini, A., McInnes, C. J., Buttner, M., Rziha, H. J., McCaughan, C. A., Fleming, S. B., Ueda, N., & Nettleton, P. F. (2002). Vascular endothelial growth factors encoded by orf virus show surprising sequence variation but have a conserved, functionally relevant structure. Journal of General Virology, 83, 2845-2855.

Imlach, W., McCaughan, C. A., Mercer, A. A., Haig, D. M., & Fleming, S. 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, 1049-1058.

Haig, D. M., Thomson, J., McInnes, C. J., Deane, D. L., Anderson, I. E., McCaughan, C. A., Imlach, W., Mercer, A. A., & 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.

Savory, L. J., Stacker, S. A., Fleming, S. B., Niven, B. E., & Mercer, A. A. (2000). Viral vascular endothelial growth factor plays a critical role in orf virus infection. Journal of Virology, 74(22), 10699-10706.

Deane, D., McInnes, C. J., Percival, A., Wood, A. R., Thomson, J., Lear, A., … Fleming, S. B., Mercer, A. A., & Haig, D. M. (2000). Orf virus encodes a novel secreted protein inhibitor of granulocyte-macrophage colony-stimulating factor and interleukin-2. Journal of Virology, 74(3), 1313-1320.

Fleming, S. B., Haig, D. M., Nettleton, P., Reid, H. W., McCaughan, C. A., Wise, L. M., & 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.

Fleming, S. B., Haig, D. M., Nettleton, P. F., Reid, H. W., McCaughlan, C. A., Wise, L. M., & Mercer, A. A. (2000). Sequence and functional analysis of a homolog of interleukin-10 encoded by the parapoxvirus, orf virus. Virus Genes, 21(1/2), 85-90.

Haig, D. M., & Fleming, S. B. (1999). Immunomodulation by virulence proteins of the parapoxvirus orf virus. Veterinary Immunology & Immunopathology, 72, 81-86.

Wise, L. M., Veikkola, T., Mercer, A. A., Savory, L. J., Fleming, S. B., Caesar, C., … Stacker, S. A. (1999). Vascular endothelial growth factor (VEGF)-like protein from orf virus NZ2 binds to VEGFR2 and neuropilin-1. PNAS, 96(6), 3071-3076. doi: 10.1073/pnas.96.6.3071

Fleming, S. B., McCaughan, C. A., Andrews, A. E., Nash, A. D., & Mercer, A. A. (1997). A homolog of interleukin-10 is encoded by the poxvirus orf virus. Journal of Virology, 71(6), 4857-4861.

Mercer, A. A., Fleming, S. B., Robinson, A., Nettelton, P., & Reid, H. W. (1997). Molecular genetic analysis of parapoxviruses pathogenic for humans. Archives of Virology, Suppl 13, 25-34.

Mercer, A. A., Lyttle, D. J., Whelan, E., Fleming, S. B., & Sullivan, J. T. (1995). The establishment of a genetic map of orf virus reveals a pattern of genomic organisation that is highly conserved among divergent poxviruses. Virology, 212, 698-704.

Fleming, S. B., Lyttle, D. J., Sullivan, J. T., Mercer, A. A., & Robinson, A. J. (1995). Genomic analysis of transposition-deletion variant of orf virus reveals a 3.3 kbp region of non-essential DNA. Journal of General Virology, 76, 2969-2978.

Sullivan, J. T., Fleming, S. B., Robinson, A. J., & Mercer, A. A. (1995). Sequence and transcriptional analysis of a near-terminal region of the orf virus genome. Virus Genes, 11, 21-29.

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Journal - Research Other

Mo, M., Fleming, S. B., & Mercer, A. A. (2010). Changing pace: Viral mimicry of an anaphase promoting complex subunit [Editorial]. Cell Cycle, 9(4), 632-633.

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