Genotype 1 and Genotype 2 Bovine Noroviruses Are Antigenically Distinct but Share a Cross-Reactive Epitope with Human Noroviruses

Abstract

The bovine enteric caliciviruses Bo/Jena/1980/DE and Bo/Newbury2/1976/UK represent two distinct genotypes within a new genogroup, genogroup III, in the genus Norovirus of the family Caliciviridae. In the present study, the antigenic relatedness of these two genotypes was determined for the first time to enable the development of tests to detect and differentiate between both genotypes. Two approaches were used. First, cross-reactivity was examined by enzyme-linked immunosorbent assay (ELISA) using recombinant virus-like particles (VLPs) and convalescent-phase sera from calves infected with either Jena (genotype 1) or Newbury2 (genotype 2). Second, cross-reactivity was examined between the two genotypes with a monoclonal antibody, CM39, derived using Jena VLPs. The two genotypes, Jena and Newbury2, were antigenically distinct with little or no cross-reactivity by ELISA to the heterologous VLPs using convalescent calf sera that had homologous immunoglobulin G titers of log 10 3.1 to 3.3. CM39 reacted with both Jena and heterologous Newbury2 VLPs. The CM39 epitope was mapped to nine amino acids ( ). Molecular modeling showed that the CM39 epitope was located within the NH 2 -terminal arm inside the virus capsid. Surprisingly, CM39 also reacted with VLPs from two genogroup II/3 human noroviruses by ELISA and Western blotting. Thus, although the bovine noroviruses Jena and Newbury2 corresponded to two distinct antigenic types or serotypes, they shared at least one cross-reactive epitope. These findings have relevance for epidemiological studies to determine the prevalence of bovine norovirus serotypes and to develop vaccines to bovine noroviruses.

Exposure to Human and Bovine Noroviruses in a Birth Cohort in Southern India from 2002 to 2006

“…The low value of Spearman's rank correlation indicated a moderate cross-reactivity of antibodies against NoV GIII to NoV GI and GII, but this alone could not explain the observed seroreactivity to bovine VLPs. This is similar to other studies which show limited cross-reactivity between human and bovine NoV strains (14,15,21,34). The differences in the prevalence rates of antibody to the VLPs tested likely indicate different levels of exposure to these viruses, with significant differences in exposure between human genogroups and bovine NoVs.…”

Multiple Antigenic Sites Are Involved in Blocking the Interaction of GII.4 Norovirus Capsid with ABH Histo-Blood Group Antigens

“…Several cross-reactive MAbs have been described for noroviruses, and epitopes for most of them have been mapped within the most conserved regions of the norovirus capsid protein (C-terminal P or S domain). As suggested previously, cross-reactive MAbs could potentially be used in diagnostic assays (3,24,36,46,51); however, Oliver et al (45) described a cross-reactive MAb that recognized a linear epitope in the S domain of the VLPs from bovine noroviruses that did not detect native virions in fecal samples from experimental animals. They proposed that because the S domain forms the innermost domain of the capsid, the epitope is not accessible in native virions.…”

“…Several cross-reactive MAbs have been identified, and most of them have been mapped to the S domain or the C-terminal region of the P1 domain (3,4,35,45,46,51,65,66). It has been reported that certain MAbs block the interaction of VLPs with cells or synthetic HBGA (38,43), and two HBGA-blocking sites were recently mapped (11,37).…”

Genetic heterogeneity of porcine enteric caliciviruses identified from diarrhoeic piglets

“…Also, antibodies to marine and terrestrial vesiviruses and vesivirus genome sequences have been detected in blood donors in the United States [13]. Animal enteric caliciviruses genetically related to human NoVs and SaVs have been detected in pigs and cows [2,[14][15][16][17][18][19][20][21]. Antibodies to human NoV have been detected in pigs and antibodies to bovine NoV have been detected in humans [22,23].…”