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

Abstract

Human norovirus (NoV) research greatly relies on cell culture-propagable surrogate caliciviruses, including murine NoVs and the prototype 'recovirus' (ReCV), Tulane virus. However, the extreme biological diversity of human NoVs 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 NoVs, G1 ReCVs were separated into three genotypes, with variable organization of the three open reading frames. Interestingly, crossneutralization 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 G1.2 ReCV serotypes (12%) was less than the minimum 13 % difference established between NoV genotypes. Interestingly, one of the G1.3 ReCVs was equally neutralized by antisera raised against the G1.3 (6 % aa difference) and G1.1 (25 % aa difference) representative strains. These results imply the existence of a large number of human NoV serotypes, but also shared crossneutralization 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.

Tulane Virus as a Potential Surrogate To Mimic Norovirus Behavior in Oysters

“…TV also recognizes neutral HBGAs and displayed a tissue distribution that was more closely aligned with that of NV than with that of MgV, although it did not bioaccumulate as efficiently as NV. Since there are significant differences in the tissue distribution and retention of different NoV strains in oysters (26), the availability of diverse, cell cultureadapted ReCVs representing different HBGA binding patterns makes this surrogate even more attractive for modeling NoV bioaccumulation in shellfish (29,60). The TV bioaccumulation efficiency obtained here is more comparable to those obtained for GII NoVs in our previous study, where the bioaccumulation efficiency of a GII.3 NoV was 0.1 to 0.5% at 1 h and 0.9 to 4.1% at 24 h. Moreover, a GII.4 NoV strain (Ͻ0.1%) bioaccumulated very poorly in oysters over 24 h (26), consistent with the recent demonstration that TV recognizes the A type 3 and B HBGAs (61).…”

“…Similar to the case for NoVs, the route of ReCV transmission is fecal-oral, and ReCVs are shed in large quantities in the stools of infected animals. Moreover, ReCVs also recognize HBGAs and can be grown to high titers in cultured cells, making them a valuable surrogate for the uncultivable human NoVs (29). Considering these features, in this study, we selected TV as a potential NoV surrogate and mengovirus (MgV) as a virus control to investigate NoV persistence in oysters.…”

Norovirus vaccines: Correlates of protection, challenges and limitations

“…Due to all the above, this model is thought to reflect the diversity of human NoVs, the reproducibility of the disease symptoms, the feasibility of testing the susceptibility to infection and attachment to receptors as a result of the availability of susceptible and non-susceptible cell lines. 115,120 The non-human primate model is genetically and immunologically close to humans and consequently could be the next-generation model to characterize and investigate NoV infection and potential vaccines.…”

Prevalence of Recovirus-Neutralizing Antibodies in Human Serum Samples

“…Recently, the characterization of 10 cell culture-adapted genogroup 1 ReCV isolates, including the Tulane virus, revealed the existence of at least four serotypes (4). This presented the opportunity for further investigation of ReCV infections in humans and their possible zoonotic origin by evaluating seroprevalence against different serotypes and in different human populations.…”

“…ReCVs not only can be grown in cell culture, but evolutionarily and biologically are closely related to human noroviruses (NoV) and are a promising surrogate for human NoV research (3)(4)(5).…”