9TCC

African Horse Sickness Virus serotype 4 VP2 homotrimer

Summary for 9TCC

• Entry DOI: 10.2210/pdb9tcc/pdb
• EMDB information: 55790
• Descriptor: Outer capsid protein VP2, ZINC ION (2 entities in total)
• Functional Keywords: viral protein, serotype determinant, protective inmmunity
• Biological source: African horse sickness virus 4
• Total number of polymer chains: 3
• Total formula weight: 377457.85

Authors

Martinez-Castillo, A.,Aebischer, A.,Fu, L.,Breard, E.,Zientara, S.,Kortekaas, J.,Beer, M.,Abrescia, N.G.A. (deposition date: 2025-11-21, release date: 2026-07-22)

Primary citation

Martinez-Castillo, A.,Aebischer, A.,Toneatti, P.,Fu, L.,Vitour, D.,Sailleau, C.,Hoffmann, B.,Franzke, K.,Eschbaumer, M.,Weber, S.,Calvo Pinilla, E.,Ortego, J.,Gil-Carton, D.,Breard, E.,Zientara, S.,Kortekaas, J.,Beer, M.,Abrescia, N.G.
Cryo-EM structure of African horse sickness virus VP2 receptor-binding protein enables nanoparticle vaccine design.
Nat Commun, 2026

PubMed Abstract: African horse sickness virus (AHSV) is a lethal equine pathogen with no licensed vaccine other than vaccines containing attenuated virus, which pose safety risks. Endemic to sub-Saharan Africa, AHSV has caused epizootics in Spain and Portugal, Cyprus, Morocco, the Middle East, India and Pakistan and, most recently, Thailand. Here, we resolve the 3.11 Å cryo-EM structure of full-length VP2 from AHSV serotype 4, adopting its native triskelion architecture and shedding light on an α-helical domain anchoring the triskelion core, which is absent in other structurally characterized orbiviruses. Structure-guided mapping identified a subdomain of VP2 as a key target of neutralizing antibodies. Displayed on nanoparticles using the SpyCatcher/SpyTag technology, the domain conferred complete protection from clinical disease after viral challenge infection in mice and elicited robust and long-lasting immune responses in horses, the target species of AHSV. These findings provide a structural blueprint for the next generation of recombinant vaccines against AHSV and related orbiviruses.

PubMed: 42401561
DOI: 10.1038/s41467-026-75067-9

Experimental method

ELECTRON MICROSCOPY (3.11 Å)