Molecular biology of Orbiviruses

Research Leader: Prof Jacques Theron

ORCiD
Scopus Author ID

Research Focus:

Our research group is interested in the genetic basis of virulence, disease and pathogenicity of African horse sickness virus (AHSV), a virus belonging to the Orbivirus genus of the family Reoviridae. AHSV causes a severe disease in equids that shows a broad spectrum of clinical symptoms, and varying degrees of pathogenesis in different tissues. AHSV however has no negative effect on its insect vector the Culicoides midge, and causes no discernible cytopathic effect (CPE) on insect cells in tissue culture. Many aspects of the AHSV lifecycle remain unclear, specifically the determinants of its cellular pathogenicity in the mammalian host. Questions of particular interest are how the virus differentially interacts with mammalian and insect cell types, the role of non-structural proteins in the virus replication cycle and the cell death pathways activated in host cells. Our research group addresses these questions using different approaches. We study structure-function relationships in individual AHSV proteins, and the extent to which variation in a single protein may contribute to virus phenotypic properties. This is based on working with prokaryotic and eukaryotic gene expression systems. The research also utilizes different AHSV strains and generates genomic reassortants where one or more genes are exchanged between two parental viruses. This is complemented by the use of a reverse genetics system for AHSV that allows generation of genetically manipulated viruses. These viruses are assessed in tissue culture models, where interaction of different viral proteins, interaction of viral and cellular proteins, and host cell responses can be studied.

Co-investigators:

Dr FF Maree, Transboundary Animal Diseases (TAD) Unit, Onderstepoort Veterinary Institute, Agricultural Research Council, South Africa.

Prof V van Staden, Department of Biochemistry, Genetics and Microbiology, Division of Genetics, University of Pretoria, South Africa.

Supervised Students:

MSc:

Miss N Kleinhans
Miss A Buyens
Mrs G Roebuck
Mr MF Martins
Ms S Pretorius

PhD:

Mr P Kara
Ms T Malinga
Mr M Rathogwa
Ms MV Mamabolo
Mrs EM Botha

Selected Publications

Vermaak, E., Conradie, A.M., Maree, F.F. and Theron, J. (2016). African horse sickness virus infects BSR cells through macropinocytosis. Virology 497, 217-232.
Conradie, A.M., Stassen, L., Huismans, H., Potgieter, C.A. and Theron, J. (2016). Establishment of different plasmid only-based reverse genetics systems for the recovery of African horse sickness virus. Virology 499, 144-155.
Vermaak, E., Maree, F.F. and Theron, J. (2017). The Culicoides sonorensis inhibitor of apoptosis 1 protein protects mammalian cells from apoptosis induced by infection with African horse sickness virus and bluetongue virus. Virus Research 232, 152-161.
Ferreira-Venter, L., Venter, E., Theron, J. and van Staden, V. (2019). Targeted mutational analysis to unravel the complexity of African horse sickness virus NS3 function in mammalian cells. Virology 531, 149-161.
Chitray, M., Kotecha, A., Nsamba, P., Ren, J., Maree, S., Ramulongo, T., Paul, G, Theron, J., Fry, E.E., Stuart, D.I. and Maree, F.F. (2020) Symmetrical arrangement of positively charged residues around the 5-fold axes of SAT type foot-and-mouth disease virus enhances cell culture of field viruses. PLoS Pathogens 16(9): e1008828.

Links:

https://www.researchgate.net/profile/Jacques-Theron-6

Published by Annel Smit

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