Genetic Mapping of a Highly Variable Norovirus GII.4 Blockade Epitope: Potential Role in Escape from Human Herd Immunity

摘要: Noroviruses account for 96% of viral gastroenteritis cases worldwide, with GII.4 strains responsible >80% norovirus outbreaks. Histo-blood group antigens (HBGAs) are binding ligands, and antigenic preferential HBGA profiles vary over time as new emerge. The capsid P2 subdomain facilitates binding, contains neutralizing antibody epitopes, likely evolves in response to herd immunity. To identify amino acids regulating differences time, we created chimeric virus-like particles (VLPs) between the GII.4-1987 GII.4-2006 by exchanging putative epitopes characterized their using anti-GII.4-1987 -2006 mouse monoclonal antibodies (MAbs) polyclonal sera, 1988 outbreak human synthetic HBGAs. exchange 393 395 resulted altered compared parental strains. Introduction residues 294, 297 298, 368, 372 (epitope A) into reactivity three MAbs reduced four anti-GII.4-2006 MAbs. also blocked VLP-HBGA interaction, while an blocking did not, indicating that epitope A comprise a potential GII.4-2006. We tested GII.4-1987-immunized sera ability block interaction found contribute significantly blockade response. Our data provide insights help explain emergence epidemic may aid development therapeutics, predict future