Relationship between genotypes and serotypes of genogroup 1 recoviruses: a model for human norovirus antigenic diversity

Human norovirus (NoV) research greatly relies on cell culture-propagable surrogate caliciviruses, including murine No Vs and the prototype 'recovirus' (ReCV), Tulane virus. However, the extreme biological diversity of human No Vs cannot be modelled by a uniform group of viruses or single isolate. Based on a diverse group of recently described ReCVs, a more advanced model reflecting human NoV biological diversity is currently under development. Here, we have reported the genotypic and serotypic relationships among 10 G1 ReCV isolates, including Tulane virus and nine other recent cell culture-adapted strains. Based on the amino acid sequences of virus capsid protein, VP1, and classification constraints established for No Vs, G1 ReCVs were separated into three genotypes, with variable organization of the three open reading frames. Interestingly, cross-neutralization plaque assays revealed the existence of four distinct serotypes, two of which were detected among the G1.2 strains. The amino acid (aa) difference between the two 01.2 ReCV serotypes (12%) was less than the minimum 13% difference established between NoV genotypes. Interestingly, one of the 01.3 ReCVs was equally neutralized by antisera raised against the 01.3 (6 % aa difference) and 01.1 (25 % aa difference) representative strains. These results imply the existence of a large number of human NoV serotypes, but also shared cross-neutralization epitopes between some strains of different genotypes. In conclusion, the newly developed ReCV surrogate model can be applied to address biologically relevant questions pertaining to enteric CV diversity.