Immunome Research
Open Access
ISSN: 1745-7580
+44-77-2385-9429
ISSN: 1745-7580
+44-77-2385-9429
Gehan Ahmed Mostafa
Ain Shams University, Egypt
Posters-Accepted Abstracts: Immunome Res
Noroviruses are positive-sense, single-stranded RNA viruses and are a major cause of gastroenteritis worldwide. Norovirus capsid protein can be subdivided into a shell (S) domain, hinge (H) region, and protruding (P) domain. The P domain contains the most genetically variable region on the capsid and binding site for histo-blood group antigens (HBGAs). Despite their discovery over 40 years ago, there are still no vaccines or antivirals. In this project we characterized binding of several VHHs (nanobodies) to human norovirus capsid. One nanobody, Nano-85, was broadly reactive, while the others, Nano-25 and Nano-27, were strain specific. All nanobodies bound to the lower region on the P domain and had nanomolar affinities. The Nano-85 binding site mainly comprised highly conserved amino acids among the genetically distinct genogroup II noroviruses. Several of the conserved residues also were recognized by a broadly reactive monoclonal antibody, which suggested this region contained a dominant epitope. Superposition of the P domain nanobody complex structures into a cryoelectron microscopy particle structure revealed that both nanobodies bound at occluded sites on the particles. The flexible hinge region likely permitted a certain degree of P domain movement on the particles in order to accommodate the nanobodies. Interestingly, the Nano-85 binding interaction with intact particles caused the particle disassembly in vitro. Altogether, these results suggested that the highly conserved Nano-85 binding epitope contained a trigger mechanism for particle disassembly.
Email: gehan.mostafa2000@yahoo.com