Dr Vernon Ward, Department of Microbiology and Immunology, University of Otago

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Associate Professor Vernon Ward

Ward Laboratory
Insect Virology and Caliciviruses

Research Interest: Molecular Virology
Year of Appointment: 1993
Training: BSc(Hons) PhD(Otago)

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. Specific project areas are:

Caliciviruses

• 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 the study of human noroviruses.

RHDV virus-like particles

RHDV VLP cryoEM reconstruction (Dr Tom Smith, Donald Danforth Centre, St Louis, MO, USA)

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 Assoc. Prof. Margaret Baird and Dr Sarah Young in the Department of Microbiology & Immunology.

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.

Noroviruses

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 the University of Otago

Recent Publications on Caliciviruses:

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).

Insect Virology

• 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

Scanning EM of Wiseana 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).

This research is supported by the Marsden Fund

Centrifuge pellet of purified iridovirus

(IIV-9)

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.

This research is supported by the Marsden Fund

40nm Thosea asigna virus particles

Tetraviruses: This group of RNA viruses is characterised by a diverse cluster of viruses represented by a T=4 icosahedral capsid. Genome analysis has shown some of these viruses to possess a permuted order to the core motifs characterising the palm domain of the template dependant polymerases. This permutation has subsequently been identified in other viruses such as the dsRNA birnaviruses and represents a new and ancient lineage of RNA polymerase. This research is in collaboration with international researchers, in particular Dr Karl Gordon, CSIRO, Australia, and Dr Alexander Gorbalenya, Leiden University, The Netherlands.

Selected Recent Publications in Insect Virology:

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).

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).

Radloff, C., Vaia, R.A. Brunton, J., Bouwer, G.T., and Ward, V.K. Metal nanoshell assembly on a virus bioscaffold. Nano Letters 5:1187-1191 (2005).

Young, V.L., Simpson, R.M., and Ward, V.K. Characterization of an exochitinase from Epiphyas postvittana nucleopolyhedrovirus (family Baculoviridae). Journal of General Virology 86: 3253-3261 (2005)

Postgraduate Research

The laboratory is actively involved in supporting postgraduate student research with current students working on projects in the areas 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 Assoc. Prof. Margaret Baird and Dr Sarah Young.

• P. Wong, MSc (with Distinction), Whole genome sequencing of WIV, 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 (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

• E. Baker, BAppSc(Hons), Norovirus orf4, 2007

• N. Sitasuwan, BAppSc(Hons), Virus-like particles of murine norovirus, 2007

• J-W Chiu, BAppSc(Hons), Chitinase’s little helper, 2007.

Key Undergraduate Teaching Roles

Course Director, Molecular Biotechnology
http://www.otago.ac.nz/appliedscience/bappsc/mobi.php

Course Coordinator, MICR336, Microbial Biotechnology
http://microbiology.otago.ac.nz/dept/courses/micr336.html

Course Coordinator, MICR337, Virology
http://microbiology.otago.ac.nz/dept/courses/micr337.html

Other Activities

Co-convenor, Virology Otago
http://mrna.otago.ac.nz/Virology/Virology.html

Academic lead, Otago component, Partnering for Innovation Programme:
http://pfi.otago.ac.nz