Current Position:
Professor of Virology, Department of Microbiology & Immunology, University of Otago.
Recent roles:
2014-2019, Dean, School of Biomedical Sciences, University of Otago.
2012-2014, Head of Department of Microbiology & Immunology, University of Otago.
2015-2017, Acting Director, Otago Genomics and Bioinformatics Facility (OGBF).
2008-present, NZ Representative, International Committee for the Taxonomy of Viruses.
2013-2018, Chair of Management Committee, Hercus Taieri Resource Unit, University of Otago.
2013- present, Project Owner, Chair of Executive Planning Team and member of University Project Steering Committee, Eccles Building project, University of Otago.
2017- present, Member, Project Steering Committee, University of Otago, Christchurch Campus Redevelopment Project.
2011-2017, Executive Committee, Australasian Virology Society.
2015-2019, Member NZ International Science Festival Executive Committee.
2015-2019, Member, Otago Medical Research Foundation Executive Committee
Viral pathogenesis, Molecular virology, Applied immunology, Host pathogen interactions
Viruses are well known for their ability to cause disease and there is an ongoing need to develop treatments for a range of viruses. Understanding the interactions between a virus and its host cell and the mechanisms of viral replication are important for the development of antiviral agents. In addition, the diversity of structure and replication found in viruses offers opportunities for exploiting the biology and properties of viruses for beneficial purposes. Our research investigates the replication of viruses and their interaction with the host for the development of antiviral agents and exploitation of virus properties for beneficial purposes.
Due to recent acceptances, the lab is NOT accepting new MSc or PhD students.
Ward Lab 2021
Yasmin, Geena, Vivienne, Simone, Scott, Vernon, Roman, Alice, Alice, Nick
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Vivienne Young |
Postdoctoral Fellow |
Lohitha Putha Assistant Research Fellow |
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Postgraduate students |
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| Geena McKenzie-Goldsmith PhD Student |
Scott Clifford PhD Student |
Nicholas Yang PhD Student |
Matt Edwards PhD Student |
(RHDV VLP cryoEM reconstruction image: Dr Tom Smith, Donald Danforth Centre, St Louis, MO, USA).
Our research group predominantly studies caliciviruses. Caliciviruses are small isometric RNA viruses with a single-stranded, positive-sense RNA genome. There are a wide range of viruses in the Caliciviridae family with members infected a wide range of animals in many different environments.
Two well-studied groups of caliciviruses are the noroviruses, well-known for their ability to cause gastrointestinal disease, and lagoviruses, well-known for their ability to cause disease in rabbits and other lagomorphs.
The research group has a long standing interest in insect viruses and continues to routinely use the baculovirus insect cell expression system for the production of recombinant proteins.
Noroviruses
Globally, there are an estimated 699 million illnesses and over 200,000 deaths attributed to noroviruses annually. Norovirus infections result in $US60.3 billion in societal costs and $US4.2 billion in direct healthcare cost (Bartsch et al, 2016, PLoS One 11, e0151219). There is a clear need for rapid treatment in semi-closed environments such as hospitals, the military and aged care facilities, and where patients are immunosuppressed, such as during transplantation. There are no vaccines or direct-acting antiviral agents for noroviruses with this further complicated by the episodic emergence of pandemic strains through recombination and drift. There is an urgent need for norovirus antivirals that can be administered at the first sign of symptoms and as a prevention for spread.
Despite new systems becoming available, human noroviruses remain challenging to replicate in culture. The use of viral replicons and model viruses such as the murine norovirus continue to be important for investigating viral replication, host-pathogen interactions and the development of anti-viral agents. These systems will complement new human norovirus culture systems as they become more prevalent.
Goals of this research:
This research is supported by an MBIE Endeavour Programme Grant, The Maurice Wilkins Centre for Molecular Biodiscovery and the University of Otago.
Rabbit hemorrhagic disease Virus-like Particles (RHDV VLP)
The over-expression of the major capsid protein(s) of a range of viruses leads to the assembly of Virus-Like Particles (VLP). A well known example is the Human papilloma virus VLP that is used as a vaccine against papillomavirus infection and cervical cancer. VLP are excellent particulate vaccines.
Our interest in VLP is to use these complex particles as carriers for subunit vaccines. We were looking for a VLP that would not meet pre-existing immunity in preclinical experiments or during clinical application. We did not want to use VLP that might complicate future vaccination regimes. We wanted to be able to generate both humoral and cell-mediated immunity to provide a broadly applicable vaccine delivery platform.
We have developed the VLP derived from RHDV as a vaccine carrier for immune epitopes and proteins. This carrier is suitable for cross-presentation of MHC-I epitopes to the immmune system for the generation of cell-mediated immunity and is an effective carrier of epitopes for antibody generation through multiple delivery routes.
Goals of this research:
Section of Epiphyas postvittana NPV occlusion body
Baculoviruses are a core competency of the laboratory with a long history of research of these viruses for biological control of insect pests. The laboratory uses the baculovirus expression vector system as a standard laboratory tool for the eukaryotic expression of recombinant proteins, including the RHDV VP60 protein for production of virus-like particles and various norovirus proteins
We also maintain an interest in insect iridoviruses.
Eruera, A.-R., McSweeney, A.M., McKenzie-Goldsmith, G.M., Opel-Reading, H.K., Thomas, S.X., Campbell, A.C., Stubbing, L., Siow, A., Hubert, J.G., Brimble, M.A., Ward, V.K., and Krause, K.L.. Crystal Structure of Inhibitor-Bound GII.4 Sydney 2012 Norovirus 3C-Like Protease. Viruses 15, 2202. (2023).
Wobus, C.E., Peiper, A.M., McSweeney, A.M., Young, V.L., Chika, M., Lane, M.S., Lingemann, M., Deerain, J.M., Strine, M.S., Alfajaro, M.M., Helm, E.W., Karst, S.M., Mackenzie, J.M., Taube, S., Ward, V.K., and Wilen, C.B. Murine norovirus: additional protocols for basic and antiviral studies. Current Protocols 3, e828. Doi: 10.1002/cpz1.828 (2023).
Stubbing, L.A., Hubert, J.G., Bell-Tyrer, J., Hermant, Y.O., Yang, S.H., McSweeney, A.M., McKemzie-Goldsmith, G., Ward, V.K., Furkert, D.P., and Brimble, M.A. P1 Glutamine Isosteres in the Design of Inhibitors of 3C/3CL Protease of Human Viruses of the Pisoniviricetes Class. RCS Chemical Biology, 4:533-547 (2023)
Sparrow, K.J., Shrestha, R., Wood, J.M., Clinch, K., Hurst, B.L., Wang, H., Gowen, B.B., Julander, J.G., Tarbet, E.B., McSweeney, A.M., Ward, V.K. Evans, G.B., Harris, L.D. An isomer of galidesivir that potently inhibits influenza viruses and members of the Bunyavirales order. ACS Medicinal Chemistry Letters. 14(4):506-513 (2023).
Mirabelli, C., Jones, M.K., Young, V.L., Kolawole, A.O., Owusu, I., Shan, M., Abuaita, B., Turula, H., Trevino, J.G., Grigorova, I., Lundy, S.K., Lyssiotis, C.A., Ward, V.K., Karst, S.M., and Wobus, C.E. Human norovirus triggers primary B cell immune activation in vitro. MBio 13(2) e0017522 (2022).
Eruera, A.-R.; McSweeney, A.M.; McKenzie-Goldsmith, G.M.; Ward, V.K. Protein Nucleotidylylation in +ssRNA Viruses. Viruses 13:1549 (2021).
McSweeney, A.M., Young, V.L., and Ward, V.K. Norovirus VPg binds RNA through a conserved N-terminal K/R basic patch. Viruses 13:1282 (2021).
Campbell, K., Young, V.L., Donaldson, B.C., Woodall, M.J., Shields, N.J., Walker, G.F., Ward, V.K. and Young, S.L. Vaccines 9:463 (2021).
Dowlath, S., Campbell, K., Al-Barwani, F., Young, V.L., Young, S.L., Walker, G.F., Ward, V.K. Dry Formulation of Virus-Like Particles in Electrospun Nanofibers. Vaccines 9:213 (2021).
Krause, K.L., Furneaux, R., Benjes, B., Brimble, M., Davidson, T., Denny, W., Harris, L., Hinkley, S., Tyler, P., Ussher, J., and Ward, V. The post-lockdown period should be used to acquire effective therapies for future resurgence in SARS-CoV-2 infections. N.Z. Med. J. 133, 107-111. (2020).
Thomson, N. A., Howe, L., Weidgraaf, K., Thomas, D. G., Young, V., Ward, V. K., Munday, J. S. Fells catus papillomavirus type 2 virus-like particle vaccine is safe and immunogenic but does not reduce FcaPV-2 viral loads in adult cats. Veterinary Immunology and Immunopathology 213: 109888, doi.org/10.1016/j.vetimm.2019.109888 (2019).
Kim, S.H., Mercer, A., Mitchell, A., de Miranda, J.R., Ward, V., Mondet, F., and Bostina, M. Viral infections induced alterations of antennal epithelium ultrastructure in honey bees. Journal of Invertebrate Pathology. 168:107252.(2019).
Thomson, N. A., Howe, L., Weidgraaf, K., Thomas, D. G., Young, V., Ward, V. K., Munday, J. S. Fells catus papillomavirus type 2 virus-like particle vaccine is safe and immunogenic but does not reduce FcaPV-2 viral loads in adult cats. Veterinary Immunology and Immunopathology 213: 109888, doi.org/10.1016/j.vetimm.2019.109888 (2019).
McSweeney, A., Davies, C., and Ward, V.K. Cell cycle arrest is a conserved function of norovirus VPg proteins. Viruses 11:217 (2019).
Kramer, K., Al-Barwani, F, Baird, M.A., Young, V.L., Larsen, D.S., Ward, V.K. and Young, S.L. Functionalisation of virus-like particles enhances anti-tumour immune responses. Journal of Immunological Research. DOI: 10.1155/2019/5364632, 10 pages (2019).
Donaldson, B., Lateef, Z., Walker, G.F., Young, S.L., and Ward, V.K. Virus-like particle vaccines: immunology and formulation for clinical translation. Expert Reviews Vaccines. 17:9, 833-849 (2018).
Donaldson, B., Al-Barwani, F., Pelham, S.J., Young, K., Ward, V.K., and Young, S.L. Multi-target chimaeric VLP as a therapeutic vaccine in a model of colorectal cancer. Journal for ImmunoTherapy of Cancer. 5:69 (2017).
Li, K., Donaldson, B., Young, V., Ward, V., Jackson, C., Baird, M., and Young, S.L. Adoptive cell therapy with CD4+ T help1 cells and CD8+ cytotoxic T cells enhance complete rejection of an established tumour, leading to generation of endogenous memory response to non-targeted tumour epitopes. Clinical and Translational Immunology. 6:e160 (2017)
Nicholson, L.J., Mahar, J.E., Strive, T., Zheng, T., Holmes, E.C., Ward, V.K., and Duckworth, J.A. Benign rabbit calicivirus in New Zealand. Applied and Environmental Microbiology, 83:e00090-17 (2017).
Lateef, Z., Gimenez, G., Baker, E.S., and Ward, V.K. Transcriptomic analysis of human norovirus NS1-2 protein highlights a multifunctional role. BMC genomics, 18:39 (2017).
Mahar, J.E., Nicholson, L., Eden, J.-S., Duchene, S., Kerr, P.J., Duckworth, J., Ward, V.K., Holmes, E.C., and Strive, T. Benign rabbit caliciviruses exhibit evolutionary dynamics similar to those of their virulent relatives. Journal of Virology 90:9317-9329, (2016)
Davies, C. and Ward, V.K. Expression of the NS5 (VPg) protein of murine norovirus induces a G1/S phase arrest. PLoS ONE 11(8) e0161582 (2016).
Slatter, T.L., Wilson, M., Tang, C., Campbell, H.G., Ward, V.K., Young, V.L., Van Ly, D., Fleming, N.I., Braithwaite, A.W., and Baird, M.A. Anti-tumor cytotoxicity induced by bone marrow-derived antigen presenting cells is facilitated by the tumor suppressor protein p53 via regulation of IL-12. OncoImmunology 5(3) e1112941, (2016)
Donaldson, B., Al-Barwani, F., Young, V., Scullion, S., Ward, V., and Young, S. Virus-like particles, a versatile subunit vaccine platform. In: Advances in Delivery Science and Technology: Subunit Vaccine Delivery. Foged, C., Rades, T., Perrie, Y., and Hook, S. Eds. Springer, 2015 Chapter 9, pp159-180 [ISBN 978-1-4939-1417-3].
Davies, C., Brown, C.B., Westphal, D., Ward, V.K. Murine norovirus replication induces a G0/G1 cell cycle arrest in asynchronous cells. Journal of Virology 89(11) 6057-6066, (2015).
Chiu, E., Hijnen, M., Bunker, R., Boudes, M., Rajendren, C., Aizel, K., Olieric, V., Schulze-Briese, C., Mitsuhashi, W., Young, V., Ward, V.K., Bergoin, M., Metcalf, P., and Coulibaly, F. Strcutural basis for the virulence activity and in vivo crystallization of viral spindles. Proceedings of the National Academy of Sciences, USA. 112(13) 3973-3978, doi10.1073/pnas.1418798112 (2015).
Herod, M.R., Prince, C.A., Skilton, R.J., Ward, V.K., Cooper, J.B., and Clarke, I.N. Structure-based design and functional studies of novel noroviral 3C protease chimeras offers insight into substrate specificity. Biochemical Journal, 464:461-472 (2014).
Al-Barwani, F., Donaldson, B., Pelham, S., Young, S.L., and Ward, V.K. Antigen Delivery by virus-like particles for immunotherapeutic vaccination. Therapeutic Delivery, 5(11), 1223-1240 (2014).
Al-Barwani, F., Young, S.L., Baird, M.A., Larsen, D.S., Ward, V.K. Mannosylation of virus-like particles enhances internalization by antigen presenting cells. PLoS ONE, 9(8): e104523 (2014).
Herod, M.R., Salim, O., Skilton, R.J., Prince, C.A., Ward, V.K., Lambden, P.R., and Clarke, I.N. Expression of the Murine norovirus (MNV) ORF1 polyprotein is sufficient to induce apoptosis in an inducible virus-free cell model. PLoS one, 9(3):e90679 (2014).
Waugh, E., Chen, A., Baird, M.A., Brown, C.B., and Ward, V.K. Characterization of the chemokine response of RAW264.7 cells to infection by murine norovirus. Virus Research 181:27-34 (2014).
Sirotkin, S., Mermet, A., Bergoin, M., Ward, V., and Van Etten, J. Viruses as nanoparticles: structure versus collective dynamics. Physical Review E. 90: e022718 (2014).
The laboratory is not currently accepting new postgraduate students.
Postgraduate students in the lab include 3 PhD students, 1 MSc student and 1 BBiomedSc(Hons) student currently being supervised on projects associated with the research outlined above. There have been 72 postgraduate degree project completions for a range of degrees by students in the laboratory. There are currently a Scientific Officer, two Postdoctoral Fellows and an Assistant Research Fellow in the laboratory (2021).
A. Eruera, PhD, Structural investigation of GII.4 human norovirus mature and precursor proteins, 2022
S. Clifford, MSc (Distinction), Targeting SARS-CoV-2 primase activity, 2022
S. Thomas, MSc (Distinction), Targeting the Human Norovirus Protease-Polymerase Precursor Protein (ProPol) 2022.
M. Edwards, BBioMedSc(Hons 1st class), Norovirus non-structural (NS) 1-2 protein processing, 2022
A. McSweeney, PhD, Murine norovirus VPg interaction with the host cell cycle, 2020.
S. Dowlath, MSc(Distinction), Stabilised virus-like particles for vaccination, 2018.
S. Thomas, BSc(Hons 1st Class), Human norovirus VPg and the cell cycle, 2018.
G. McKenzie-Goldsmith BSc(Hons 1st Class), Human norovirus propol, 2018.
L Nicholson, PhD, Rabbit biocontrol, investigating the role of rabbit caliciviruses in the epidemiology of RHDV in NZ, 2017
B. Donaldson, PhD, Development of a virus-based cDNA library vaccine for colorectal cancer, 2017
C. Davies, PhD, Norovirus regulation of the cell cycle, 2016.
F. Al Barwani, PhD, Enhancing the functionality of RHDV nanoparticles, 2015
E. Waugh, PhD, The regulation of chemokines by murine norovirus, 2015
