Binding Patterns of Human Norovirus-Like Particles to Buccal and Intestinal Tissues of Gnotobiotic Pigs in Relation to A/H Histo-Blood Group Antigen Expression

Abstract

Histo-blood group antigen (HBGA) phenotypes have been associated with susceptibility to human noroviruses (HuNoVs). Our aims were: (i) to determine the patterns of A/H HBGA expression in buccal and intestinal tissues of gnotobiotic (Gn) pigs; (ii) to determine if virus-like particles (VLPs) of HuNoV genogroup I (GI) and GII bind to A- or H-type tissues; (iii) to compare A/H expression and VLP binding patterns and confirm their binding specificities by blocking assays; (iv) to develop a hemagglutination inhibition test using buccal cells from live pigs to determine the Gn pig's A/H phenotype and to match viral strains with previously determined HuNoV VLP binding specificities; and (v) to determine the A/H phenotypes and compare these data to the infection outcomes of a previous study of 65 Gn pigs inoculated with HuNoV GII/4 strain HS66 and expressing A and/or H or neither antigen on their buccal and intestinal tissues (S. Cheetham, M. Souza, T. Meulia, S. Grimes, M. G. Han, and L. J. Saif, J. Virol. 80:10372-10381, 2006). We found that the HuNoV GI/GII VLPs of different clusters bound to tissues from four pigs tested (two A+ and two H+). The GI/1 and GII/4 VLPs bound extensively to duodenal and buccal tissues from either A+ or H+ pigs, but surprisingly, GII/1 and GII/3 VLPs bound minimally to the duodenum of an A+ pig. The VLP binding was partially inhibited by A-, H1-, or H2-specific monoclonal antibodies, but was completely blocked by porcine mucin. Comparing the A/H phenotypes of 65 HS66-inoculated Gn pigs from our previous study, we found that significantly more A+ and H+ pigs (51%) than non-A+ and non-H+ pigs (12.5%) shed virus. From the 22 convalescent pigs, significantly more A+ or H+ pigs (66%) than non-A+ or H+ pigs (25%) seroconverted.

Pathogenesis and Immune Responses in Gnotobiotic Calves after Infection with the Genogroup II.4-HS66 Strain of Human Norovirus

“…We previously confirmed that the HuNoV-HS66 strain infects Gn pigs and described its pathogenesis in Gn pigs (9,10). We also have recently delineated the immune responses to infection by the HuNoV-HS66 strain in Gn pigs (47).…”

Epochal Evolution of GGII.4 Norovirus Capsid Proteins from 1995 to 2006

“…While not causing (many) outbreaks, strains may circulate in the population and not come to the attention of surveillance, slowly accumulating mutations until the built-up genetic variety results in enough antigenic variety to be able to successfully cause (more) outbreaks and become a dominant variant. Alternatively, animal reservoirs, a limited number of which have been recognized (7,8,16), or chronically infected patients (18,34) may be places where the virus can accumulate mutations.…”

Cytokine and Antibody Responses in Gnotobiotic Pigs after Infection with Human Norovirus Genogroup II.4 (HS66 Strain)

“…We further demonstrated a similar association between the phenotype A ϩ /H ϩ of Gn pigs and the development of diarrhea and higher rates of fecal viral shedding after infection with GII. 4 HuNoV-HS66 than in Gn pigs with the non-A ϩ /H ϩ phenotype (6). However, other investigators recently showed that in contrast to NV, Snow Mountain virus (SMV) (GII.2 HuNoV) infection was not influenced by histo-blood group or secretor status, suggesting that multiple factors may influence host susceptibility to the myriad of HuNoV genotypes (18).…”