Severe Virus Infections: The Belsham group
The main aim of the work is to generate increased understanding of the biology of particular viruses that cause important diseases in animals so that improved methods of disease control can be developed. The focus is mainly on diseases that are not usually present in Europe but represent a major threat if introduced. Our interests include aspects of foot-and-mouth disease virus, African swine fever virus and coronaviruses.
We seek to enhance understanding of virus biology at the molecular level. We have extensive experience in studying foot-and-mouth disease virus and continue to use this knowledge towards the development of improved vaccines to control the disease. We can achieve the production and correct processing of the viral structural proteins so that they assemble to form virus-like particles that share antigenicity with the virus but lack its infectivity. We have recently started to make use of this experience to work on the assembly of a much more complex virus, African swine fever virus. Unusually, this virus DNA also produces polyproteins that have to be processed by a virus-encoded protease to allow virus assembly to proceed.
We have also recently extended a project on coronaviruses in animals. There are many different coronaviruses that are known, a variety of these are present in Denmark, e.g. in bats, and the recent introduction of SARS-CoV-2 into mink farms has created additional interest in this area.
We also have activities investigating the survival and the means of inactivation of viruses to assist with studies to develop improved infection control.
We actively collaborate with Statens Serum Institut on activities related to the veterinary contingency program.
We have defined new features of the processing of the FMDV capsid precursor (P1-2A) by the virus-encoded protease (3Cpro). A short motif, within one of the 4 different capsid proteins (VP1) has been identified as critical for the correct processing of the entire precursor, even single amino acid changes within this motif can prevent processing and also block virus infectivity.
We have also provided new information on the extensive recombination that can occur between different serotypes of FMDV in areas of the world where the disease is endemic. These events generate novel viruses that may have distinct properties from either parental virus.
We have analysed virus adaptation in Classical swine fever virus using full genome sequencing. In addition, we have characterized some of the bat coronaviruses present in Denmark and used full genome sequencing to analyse these viruses and also a porcine coronavirus. The same type of technology is now being applied to analyzing the SARS-CoV-2 infections in mink and in humans in Denmark (in collaboration with SSI).
Read more about our findings:
Fahnøe, U, Pedersen, AG, Johnston, CM, Orton, RJ, Höper, D, Beer, M, Bukh, J, Belsham, GJ & Rasmussen, TB. (2019) Virus adaptation following challenge of animals vaccinated against classical swine fever virus. Viruses 11(10), pii E932. https://doi.org/10.3390/v11100932.
Johnston, CM, Fahnøe, U, Lohse, L, Bukh, J, Belsham, GJ, Rasmussen, TB. (2020) Analysis of virus population profiles within pigs infected with virulent Classical Swine Fever viruses; evidence for bottlenecks in transmission but absence of tissue specific virus variants. J Virol (in press) e-pub 22 July 2020: https://doi.org/10.1128/JVI.01119-20
Jamal, SM, Nazem Shirazi, MH, Ozyoruk, F, Parlak, U, Normann, P & Belsham, GJ. (2020) Evidence for multiple recombination events within foot-and-mouth disease viruses circulating in West Eurasia. Transbound Emerg Disease 67: 979-993. doi: 10.1111/tbed.13433.
Kristensen & Belsham (2019b) Identification of plasticity and interactions of a highly conserved motif within a picornavirus capsid precursor required for virus infectivity. Sci Rep. 9(1):11747.doi: 10.1038/s41598-019-48170-9
Kristensen, T & Belsham, GJ. (2019a) Identification of a short, highly conserved, motif required for picornavirus capsid precursor processing at distal sites. PLoS Pathogens 15(1):e1007509. https://doi 10.1371/journal.ppat.1007509
Lazov, CM, Chriél, M, Baagøe, HJ, Fjederholt, E, Deng, Y, Kooi, EA, Belsham, GJ, Bøtner, A & Rasmussen, TB. (2018) Detection and characterization of distinct alphacoronaviruses in five different bat species in Denmark. Viruses 10, 486; doi:10.3390/v10090486.
Belsham, GJ, Kristensen, T & Jackson, T. (2020) Foot-and-mouth disease virus: prospects for using knowledge of virus biology to improve control of this continuing global threat. Virus Research 281:197909. epub Feb 29 2020. https://doi.org/10.1016/j.virusres.2020.197909
Olesen, AS, Belsham, GJ, Rasmussen, TB, Lohse, L, Bødker, R, Halasa, T, Boklund, A, & Bøtner, A. (2020) Potential routes for indirect transmission of African swine fever virus into domestic pig herds. Transbound Emerg Disease. 67:1472-1484. epub Mar 9 doi:10.1111/tbed.13538.
Rasmussen, TB, Boniotti, MB, Papetti, A, Grasland, B, Frossard, J-P, Dastjerdi, A, Hulst, M, Hanke, D, Pohlmann, A, Blome, S, van der Poel, WHM, Steinbach, F, Blanchard, Y, Lavazza, A, Bøtner A & Belsham, GJ. (2018) Full-length genome sequences of porcine epidemic diarrhoea virus strain CV777; use of NGS to analyse genomic and sub-genomic RNAs. PLoS ONE 13(3): e0193682 doi: 10.1371/journal.pone.0193682
Molecular virology including FMDV and ASFV including analysis of viral sequence variation, virus-host interactions and assembly of virus particles for development of new vaccines. Veterinary contingency program.
Coronaviruses in animals in Denmark. Veterinary contingency program.
Photocatalytic filter for Agricultural Biosecurity (PFAB). Innovation Fonden, DK. 9.5 M DKK.
Afrikansk svinepest: Risiko for virusspredning via smitteholdige materialer. Svineafgiftsfonden.
Research Group Leader
Graham John Belsham
Cell: +45 2175 1470
Dyrlægevej 88, building 1-09
1870 Frederiksberg C