Protein breakthrough a boost for African horse sickness vaccine development

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Researchers successfully target an interesting feature of the African horse sickness virus.
Photo by Nicholas Lucien

Researchers have targeted a unique feature of the African horse sickness virus, in a development that they say will aid vaccine development.

African horse sickness is a devastating disease, which can kill up to 95% of susceptible horses. It is caused by an orbivirus, which are complex, non-enveloped viruses with a characteristic genome contained within a core particle made up of the core proteins VP7 and VP3.

The core particle is surrounded by the structural proteins VP2 and VP5, which make up the outer capsid layer of the virion.

University of Pretoria researchers Shani Bekker, Henk Huismans and Vida van Staden, writing in the journal Viruses, said a unique characteristic of the virus’s VP7 core protein is that it is highly insoluble, and spontaneously forms crystalline particles in infected cells in horses – a feature that can also be replicated in a laboratory setting.

VP7 has the ability to reassemble into distinctive insoluble, flat, hexagonal crystalline particles during infection. The development of these crystals presents many problems for the development of vaccines against the virus.

It is unclear, they said, whether VP7 aggregation affects viral assembly or contributes to the development and progression of the disease.

The trio set out to abolish VP7 self-assembly by targeting candidate amino acid regions on the surface of VP7.

It was found that the substitution of seven amino acids resulted in the complete disruption of VP7 self-assembly, which abolished the formation of the crystalline particles. It also converted VP7  into a fully soluble protein, which still proved capable of interacting with VP3 to form core-like particles.

The work, they said, provides further insights into the formation of VP7 crystalline particles by the virus and strategies for the successful development of African horse sickness vaccines.

“It also paves the way for future research by drawing comparisons with similar viral phenomena observed in human virology.”

They continued: “Now that a version of African horse sickness virus VP7 that does not assemble into crystalline particles exists, we will generate a recombinant virus that does not form crystalline particles via reverse genetics and examine the effect and role of crystalline particle formation on African horse sickness virus replication and virulence.”

The authors said much work has gone into the generation of a soluble VP7, specifically for vaccine research and development. The insolubility of VP7 has hindered vaccine strategies to date, they said. The availability of a soluble VP7 opens fresh avenues for vaccine development, with the potential to have a significant impact.

The work reported in their paper is now subject to a patent in South Africa.

Bekker, S.; Huismans, H.; van Staden, V. Generation of a Soluble African Horse Sickness Virus VP7 Protein Capable of Forming Core-like Particles. Viruses 2022, 14, 1624. https://doi.org/10.3390/v14081624

The study, published under a Creative Common License, can read here

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