Professor Andrew Mercer

Research Interest: Virus Research
Year of Appointment: 1993
Training: BSc PhD(Otago)

Professor Mercer is a Health Research Council Senior Research Fellow and an Honorary Lecturer in the Department of Microbiology. In conjunction with fellow staff of the Virus Research Unit, his research is focused on understanding viruses at the molecular level and exploiting this information in the development of vaccines against viral diseases. The Virus Research Unit has a staff of 10 researchers and a similar number of graduate students. Their work is supported by grants from the Health Research Council, New Economy Research Fund, Cancer Society, Anderson Trust and international industry sources. Current research concentrates on orf virus and human papillomavirus.

The Virus Research Unit is directed by Professor Andy Mercer and has a staff of 10 researchers and a similar number of graduate students. Their work is supported by grants from the Health Research Council, New Economy Research Fund, Cancer Society, Anderson Trust and international industry sources. The Unit is currently working with human papilloma virus, and the parapoxvirus, orf virus.

PhD Research Project Opportunities

Opportunities for PhD research projects are currently available within the Virus Research Unit. Applicants should have excellent academic records such that they would be eligible for funding from the University of Otago PhD Scholarship scheme. Primary supervision will be provided by Prof. Andrew A. Mercer (Director), Dr. Stephen B. Fleming, Dr. Lyn M. Wise, Dr Norihito Ueda or Dr Merilyn Hibma.

Initial contact relating to any of the orf virus projects should be made with Prof. Andrew A. Mercer (andy.mercer@otago.ac.nz).

PhD projects are available on the topics outlined below.

1. Orf virus encodes an unusual RING-H2 protein that we have shown can interfere with the cellular anaphase promoting complex.
• Elucidate of this protein's ability to manipulate the cell cycle
• Using viral proteins for cancer therapy
2. Orf virus encodes a novel Bcl-2-like protein that inhibits apoptosis at the mitochondria.
• Functional analysis of the mode of apoptosis inhibition
3. We have hypothesized that the large family of poxvirus ankyrin repeat proteins carry a functional F-box and that poxviruses use these proteins to exploit the cell's ubiquitin- proteasome system.
   • Identification of the substrates and biological roles of Orf virus F-box proteins
   • Defining the function of F-box helix 3 which is absent in poxviruses
4. Poxviruses exhibit a complex maturation process
   • Analysis of the morphogenesis and structure of Orf virus using recombinant viruses, EM and MALDI.
5. Poxvirus immunomodulators are viral virulence factors with therapeutic potential. Orf virus encodes a unique chemokine binding protein (CBP), an IL-10 homolog and a unique new member of Vascular Endothelial Growth Factor (VEGF) family.
   • In vitro analysis of CBP/chemokine interactions using site-directed and natural variants of the parapoxvirus CBPs.
   • In vivo activities of CBP mutants and viral IL-10 mutants in murine models of inflammatory disease and immune cell activation and trafficking.
   • In vivo activities of Orf virus VEGF mutants in murine models of inflammatory disease, immune cell activation and trafficking, haematopoietic cell differentiation/fate and tissue regeneration.
6. Biological analysis of Orf virus non-structural genes of unknown function.
7. Parapoxviruses as vaccine delivery vehicles.
• Construction and testing of recombinant parapoxviruses that express vaccine antigens of important diseases of ruminants.

Selected Publications

Viral Ankyrin Repeat Proteins

Poxvirus ankyrin repeat proteins are a unique class of F-box proteins that associate with cellular SCF1 ubiquitin ligase complexes.  Stephanie Sonnberg, Bruce T. Seet, Tony Pawson, Stephen B. Fleming and Andrew A. Mercer. 2008. Proc. Nat. Acad. Sci. (USA) 105(31): 10955-10960.  (pdf)

A truncated 2-a-helix F-box present in poxvirus ankyrin repeat proteins is sufficient for binding the SCF1 ubiquitin ligase complex.  Stephanie Sonnberg, Stephen B. Fleming, Andrew A. Mercer.  2009. J Gen Virol 90: 1224-1228. (pdf)

Poxviral host range protein CP77 contains a F-box-like domain that is necessary to suppress of NF-κB activation by TNF-α but is independent of its host range function.  Shu-Jung Chang, Jye-Chian Hsiao, Stephanie Sonnberg, Cheng-Ting Chiang, Min-Hsiang Yang, Der-Lii Tzou, Andrew A. Mercer and Wen Chang. 2009. J Virol, 83(9): 4140-4152. (pdf)

F-box-like domains in poxvirus ankyrin repeat proteins. Andrew A Mercer, Stephen B Fleming and Norihito Ueda. (2005). Virus Genes 31(2): 127-133. (pdf)

PACR – a Cell Cycle Regulator

Cell cycle deregulation by a poxvirus partial mimic of anaphase promoting complex subunit 11. Min Mo, Stephen B Fleming, and Andrew A Mercer. 2009. Proc. Nat. Acad. Sci. (USA) 106(46): 19527-19532. (pdf)

Apoptosis inhibition

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. Dana Westphal, Elizabeth C. Ledgerwood, Joel D.A. Tyndall, Merilyn H. Hibma, Norihito Ueda, Stephen B. Fleming, and Andrew A. Mercer 2009. Apoptosis 14: 1317- 1330. (pdf)

A novel Bcl-2-like inhibitor of apoptosis is encoded by the parapoxvirus, Orf virus. Dana Westphal, Elizabeth C. Ledgerwood, Merilyn H. Hibma, Stephen B. Fleming, Ellena M. Whelan, and Andrew A. Mercer. 2007. J Virol 81(13): 7178-7188. (pdf)

Viral Vascular Endothelial Growth Factor

The C-terminus of viral vascular endothelial growth factor (VEGF) partially blocks binding to VEGF receptor-1. Marie Inder, Lyn Wise, Stephen Fleming, and Andrew Mercer. 2008. FEBS Journal 275(1): 207-217. (pdf)

Major amino acid sequence variants of viral vascular endothelial growth factor are functionally equivalent during Orf virus infection of sheep skin. Lyn M. Wise, Loreen J Savory, Nicola H Dryden, Ellena M Whelan Stephen B Fleming, Andrew A Mercer. 2007. Virus Research 128: 115-125. (pdf)

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. 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). J. Biol. Chem. 278: 38004-38014. (pdf)

Viral Interleukin -10

Orf virus IL-10 inhibits cytokine synthesis in activated human THP-1 monocytes but only partially impairs their proliferation. Lyn Wise, Catherine McCaughan, Chee Keong Tan, Andrew Mercer and Stephen Fleming. 2007. J Gen Virol 88:1677-1682. (pdf)

Maturation and function of human dendritic cells are inhibited by orf virus-encoded interleukin-10. A Chan, M. Baird, A.A. Mercer and S.B. Fleming (2006). J Gen Virol 87: 3177-3181 (pdf)

Chemokine Binding protein

Orf virus encoded chemokine binding protein is a potent inhibitor of inflammatory monocyte recruitment in a mouse skin model. Zabeen Lateef, Margaret A Baird, Lyn M Wise, Andrew A Mercer, and Stephen B Fleming. 2009. J. Gen. Virol. 90:1477-1482. (pdf)

Analysis of an orf virus chemokine-binding protein: Shifting ligand specificities among a family of poxvirus viroceptors. Bruce T. Seet, Catherine A. McCaughan, Tracy M. Handel, Andrew Mercer, Craig Brunetti, Grant McFadden, and Stephen B. Fleming. (2003). Proc. Nat. Acad. Sci. (USA) 100 (25): 15137-15142. (pdf)

General

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. Joanne L. Tan, Norihito Ueda, Andrew A. Mercer and Stephen B. Fleming. 2009. J Gen Virol. 90: 614-625. (pdf)

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, Birkhaeuser Verlag, Basel. p. 127-165.

Comparative analysis of genome sequences of three isolates of Orf virus reveals unexpected sequence variation. Andrew A. Mercer, Norihito Ueda, Sonja-Maria Friederichs, Kay Hofmann, Kate M. Fraser, Trudie Bateman and Stephen B. Fleming (2006). Virus Research, 116(1-2): 146-158. (pdf)

Construction of a recombinant Orf virus that expresses an Echinococcus granulosus vaccine antigen from a novel genomic insertion site. B.J. Marsland, D. Tisdall, D.D. Heath and A.A. Mercer. (2003). Arch. Virol. 148(3): 555-562. (pdf)