Ward Lab Research
Viruses are well known for their ability to cause disease, but the diversity of virus structure and replication offers many opportunities to exploit virus particles, their structure and their replication for beneficial purposes. My current research involves both the study of pathogenic viruses and the exploitation of virus properties for beneficial purposes.
- The development of virus-like particles from rabbit haemorrhagic disease virus for the presentation of proteins and peptides to the mammalian immune system
- The analysis of murine norovirus as a model system for human noroviruses, to study the interaction between noroviruses and their host cell
RHDV virus-like particles
Our focus is on using RHDV VLP for the presentation of peptides to the mammalian immune system, exploiting their particulate nature, ability to cross-present antigen and ease of production and manipulation.
We use our extensive experience in baculoviruses for production of the VLP and exploit a range of genetic and chemical modifications for the manipulation of the particle with peptides, whole proteins and other bioactive molecules. A key research focus supported by the Health Research Council of New Zealand is the use of the VLP cross presentation capability for the development of cell mediated immunity and protection against tumours through the delivery of tumour peptides and proteins. This multidisciplinary research involves strong immunology collaboration with Prof. Margaret Baird, Department of Microbiology & Immunology and Dr Sarah Young, Department of Pathology. (RHDV VLP cryoEM reconstruction image: Dr Tom Smith, Donald Danforth Centre, St Louis, MO, USA)
Goals of this research
- To develop RHDV VLP as a rapid and simple system for the presentation of peptides and proteins to mammalian immune systems.
- To test the utility of this VLP for a range of prophylactic and therapeutic targets, in particular for the development of cell-mediated immunity.
- To undertake structure based design and engineering of the viral particle for the optimal presentation of peptides and proteins to immune systems.
This research is supported by the Health Research Council of New Zealand, Te Kaunihera Rangahau Hauora o Aotearoa and the Ministry of Science and Innovation, Te Punaha Hiringa Whakaea, Technology Transfer Voucher Programme
Noroviruses are the most common cause of non-bacterial acute gastroenteritis with an estimated 23 million cases and 50,000 hospitalisations per year in the USA and at least 53,000 cases per year in NZ. They are a global problem causing significant morbidity, particularly in semi-closed environments such as hospitals, schools, hotels and cruise ships. Human caliciviruses (noroviruses and sapoviruses) are difficult to cultivate and manipulate. An ideal model system for the study of noroviruses is the recently described Murine norovirus (MNV). This virus replicates in mice and grows in cultured primary dendritic and continuous macrophage cells. We have recently developed the first infectious reverse genetics system for noroviruses with proven infectious virus recovery and are undertaking structural and functional studies on MNV for the development of prophylactic and therapeutic treatments for noroviruses. This research is in collaboration with Prof. Ian Clarke, University of Southampton.
Goals of this research:
- To increase our understanding of the role(s) of viral proteins and the host-virus interaction.
- To understand viral elements involved in norovirus replication
- To identify targets and systems for the development of norovirus vaccines and antivirals.
This research is supported by Lottery Health Research, Te Tahua Rangahau Hauora and the University of Otago, Te Whare Wananga o Otago
- Fundamental and applied studies of baculoviruses, iridoviruses and tetraviruses
Our Molecular Virology research works on multidisciplinary projects that include collaborations with immunologists, structural biologists and protein chemists.
Goal of this research
- To identify new applications of insect viruses through fundamental studies of their replication and biology
Section of Epiphyas postvittana NPV occlusion body
Baculoviruses: Baculoviruses form a core competency in the laboratory. We use them for the expression of recombinant proteins, including RHDV VLP, investigate their use for biocontrol of leafroller insects, study the role of viral genes, and have shown that proteins can be coupled to the surface of baculovirus particles and retain the adjuvanting properties of the particles to allow their use as particulate vaccine carriers for the immunisation of mammals. Current research includes analysis of the structural properties of natural insect virus crystals, including baculoviruses and cypoviruses in collaboration with Assoc. Prof. Peter Metcalf, School of Biological Sciences, University of Auckland. Research into the biocontrol potential of baculoviruses is undertaken in collaboration with Plant and Food Research, New Zealand (Dr Ngaire Markwick, Dr John Christeller, Dr Laurence Gatehouse).
Research into natural insect virus crystals is supported by the Marsden Fund
Iridoviruses: Iridoviruses are viruses that infect insects. This group of viruses is characterised by the physical properties of these viruses causing light to refract when passing through clusters of the virus particles. This confers the iridescent properties of these viruses. The structural basis of the iridescence is being explored for photonic and material applications. In addition, these viruses are found in many different insects around the world and an in-depth analysis and comparison of their genomes would provide an important step in the understanding of iridovirus evolution and phylogeny for this genus.
Centrifuge pellet of purified iridovirus (IIV-9)
- Li, K., Peers-Adams, A., Win, S.J., Scullion, S., Wilson, M., Young, V.L., Jennings, P., Ward, V.K., Baird, M.A., Young, S.L. Antigen incorporated in virus-like particles is delivered to specific dendritic cell subsets that induce an effective anti-tumor immune response in vivo. Journal of Immunotherapy, Manuscript Accepted (2012).
- McKee, S.J., Young, V.L., Clow, F., Hayman, C.M., Baird, M.A., Hermans, I.F., Young, S.L., Ward, V.K. Virus-like particles and a-galactosylceramide form a self-adjuvanting composite particle that elicits anti-tumor responses. Journal of Controlled Release 159:338-345 (2012).
- Baker, E.S., Luckner, S.R., Krause, K.L., Lambden, P.R., Clarke, I.N., Ward, V.K. Inherent structural disorder and dimerisation of murine norovirus NS1-2 protein. PloS one 7:e30534 (2012).
- Win, S.J., McMillan, D.G.G., Errington-Mais, F., Ward, V.K., Young, S.L., Baird, M.A., Melcher, A.A. Enhancing the Immunogenicity of Tumor Lysate-Loaded Dendritic Cell Vaccines by Canjugation to Virus-Like Particles. British Journal of Cancer 106:92-98 (2012).
- Win, S.J., Ward, V.K., Dunbar, P.R., Young, S.L., and Baird, M.A. Cross presentation of epitopes on virus-like particles by dendritic cells via the MHC-I receptor recycling pathway. Immunology and Cel Biology, 2011 doi:10.1038/icb.2010.161.
- Katpally, U., Vocc, N.R., Cavazza, T., Taube, A., Rubin, J.R., Young, V.L., Stuckey, J., Ward, V.K., Virgin, H.W., Wobus, C.E., and Smith, T.J. High resolution cryo-electron microscopy structures of MNV-1 and RHDV reveals marked flexibility in the receptor binding domains. Journal of Virology 84: 5836-5841 (2010).
- Ward, V.K., Cooke, B., Strive, T. Rabbit hemorrhagic disease virus and other lagoviruses, In: Caliciviruses: Molecular and Cellular Virology, G. Hansman, J. Jiang and K.Y. Green eds, Horizon Scientific Press, (2010).
- Peacey, M., Wilson, S., Perret, R., Ronchese, F., Ward, V.K., Young, V., Young, S.L., and Baird, M.A. Virus-like particles of Rabbit hemorrhagic disease virus can induce an anti-tumor response. Vaccine 26:5334-5337 (2008).
- Wilson, S., Baird, M.A., and Ward, V.K. Delivery of vaccine peptides by rapid conjugation to baculovirus particles. Vaccine 26:2451-2456 (2008).
- Ward, V.K., McCormick, C.J., Clarke, I.N., Salim, O., Wobus, C.E., Thackray, L.B., Virgin, H.W., and Lambden, P.R. Recovery of infectious murine norovirus using pol II-driven expression of full-length cDNA. Proceeding of the National Academy of Sciences, USA 104:11050-11055 (2007).
- Peacey, M., Wilson, S., Baird, M.A., and Ward, V.K. Versatile RHDV virus-like particles: incorporation of antigens by genetic modification and chemical conjugation. Biotechnology and Bioengineering 98:968-977 (2007)
- Young, S.L., Wilson, M., Wilson, S., Beagley, K.W., Ward, V., and Baird, M.A. Transcutaneous vaccination with virus-like particles. Vaccine 24:5406–5412 (2006).
- Wong, C.K., Young, V.L., Kleffmann, T., and Ward, V.K. Genomic and proteomic analysis of Invertebrate Iridovirus Type 9. Journal of Virology 85:7900-7911 (2011).
- Zeddam, J.-L., Gordon, K.H.J., Lauber, C., Felipe Alves, C.A., Luke, B.T., Hanzlik, T.N., Ward, V.K. and Gorbalenya, A.E. Euprosterna elaeasa virus genome sequence and evolution of the Tetraviridae family: Emergence of bipartite genomes and conservation of the VPg signal with the dsRNA Birnaviridae family. Virology 397:145-154 (2010).
- Williams, T., and Ward, V.K. Iridoviruses. In: Insect Virology. Caister Academic Press, Norfolk UK, Eds. S. Asgari and K. Johnson, Chapter 6, pp. 123-151 (2010).
- Markwick, N.P., Glare, T.R., Hauxwell, C., Li, Z., Poulton, J., Ward, J.M., Young, V.L., and Ward, V.K. The infectivity and host-range of Orgyia anartoides nucleopolyhedrovirus. Journal of Applied Entomology 134:61-71 (2010).
- Coulibaly, F., Chiu, E., Gutman, S., Rajendran, C., Haebel, P., Ikeda, K., Mori, H., Ward, V., Schulze-Briese, C., and Metcalf, P. The atomic structure of baculovirus polyhedra reveals the independent emergence of intracellular infectious crystals in DNA and RNA viruses. Proceedings of the National Academy of Sciences, USA 106:22205-22210 (2009).
- Gatehouse, H.S., Poulton, J., Markwick, N.P., Gatehouse, L.N., Ward, V.K., Young, V.L., Luo, Z., Schaffer, R., and Christeller, J.T. Changes in gene expression in the permissive larval host, lightbrown apple moth (Epiphyas postvittana, Tortricidae), in response to EppoNPV (Baculoviridae) infection. Insect Molecular Biology 18:635-648 (2009).
- Gatehouse, L.N., Markwick, N.P., Poulton, J., Young, V.L., Ward, V.K., and Christeller, J.T. Expression of two heterologous proteins depends on the mode of expression: comparison of in vivo and in vitro methods. Bioprocess and Biosystems Engineering 31: 469-475 (2008).
- Hartschuh, R.D., Wargacki, S.P., Xiong, H., Neiswinger, J., Kisliuk, A., Sihn, S., Ward, V., Vaia, R.A., and Sokolov, A.P. How rigid are viruses. Physical Reviews E 78:021907 (2008).
- Juhl, S.B., Chan, E.P., Ha, Y-H., Maldovan, M., Brunton, J., Ward, V.K., Dokland, T., Kalmakoff, J., Farmer, B., Thomas, E.L., Vaia, R.A. Assembly of Wiseana Iridovirus: Viruses for Colloidal Photonic Crystals. Advanced Functional Materials 16:1086–1094 (2006).
Lab Members and Postgraduate Students
The laboratory is actively involved in supporting postgraduate student research with 5 PhD students and 2 MSc students currently being supervised on projects associated with the research outlined above. There have been over 40 research project completions for a range of degrees by students in the laboratory, with involvement in the projects of another 10 PhD students. There are currently 11 students and staff associated with the laboratory with a number in collaboration with Prof. Margaret Baird (Department of Microbiology & Immunology) and Dr Sarah Young (Department of Pathology).
Some Recent Postgraduate Completions
E. Baker, PhD, The NS1-2 protein of murine norovirus, 2012
S. Scullion, MSc (with Credit), Investigating cytotoxic T cell responses to RHDV virus-like particles, 2012
S. Win, PhD, The use of virus-like particles as immunotherapies for cancer, 2011
S. McClintoch, BSc(Hons), Can different virus-like particles be used for prime-boost vaccination, 2011
T. Abbott, BBioMedSc(Hons), Nucleotide metabolism control by norovirus, 2010
A. Peers-Adams, BBioMedSc(Hons), Dendritic cells and VLP vaccines, 2010
P. Wong, MSc (with Distinction), Analysis of the complete genome of Wiseana iridovirus, 2009.
E. Waugh, BSc(Hons), Effects of norovirus infection upon host cell gene expression, 2009.
F. Al Barwani, BBioMedSci(Hons), Glycosylation of the RHDV VLP, 2009.
R. Rao, PGDipSci (with Distinction), Nucleic acid adjuvants for virus-like particles, 2008.
H. Guttenbrunner BAppSc(Hons), Development of a virus-like particle for murine norovirus, 2008.
M. Peacey, PhD, Rabbit haemorrhagic disease virus-like particles as vaccine carriers, 2007
S. Wilson, PhD, Virus-like particle vaccines from RHDV, 2007
G. Bouwer, MSc, RHDV VLP for the display of MOMP epitopes, 2007.
- Head of Department
- New Zealand Representative, International Committee for the Taxonomy of Viruses
- Australasian Virology Society Executive http://www.avg.org.au/