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Genomic and biological characterization of a pandemic norovirus variant GII.4 Sydney 2012

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Abstract

Genogroup II, genotype 4 noroviruses (GII.4 NoVs) are a leading cause of epidemic and sporadic acute non-bacterial gastroenteritis worldwide. In this study, we isolated a GII.4 NoV strain (designated 2015HN08) from a kid presenting with acute gastroenteritis and determined its near-complete genome sequence. We then performed sequence analysis by comparing this strain with the prototypical GII.4 strain. Virus-like particles (VLPs) derived from the major capsid protein (VP1) were expressed by using a recombinant-baculovirus expression system, and monoclonal antibodies (mAbs) were produced to compare changes in antigenic or histo-blood group antigens (HBGAs) binding sites with the previously characterized GII.4 NoV strain (JZ403). The genome of 2015HN08 was 7559 nucleotides (nt) long, excluding the poly(A) tail. Genotyping analysis indicated that this strain was a Sydney 2012 variant. In comparison with the prototype Sydney 2012 strain, there were 74, 35, and 16 differences in nucleotide sequences in ORF1, OFR2, and OFR3, causing 7, 10, and 6 amino acid (aa) changes, respectively. Expression of VP1 led to successful assembly of VLPs, as demonstrated by electron microscopy. Screening of hybridoma cell supernatants with an in vitro VLP–HBGAs binding blockade assay led to the identification of a cell clone 3G10 that exhibited HBGA-blocking effects. This mAb also exhibited blocking effects against JZ403 strain, suggesting maintenance of the antigenic site and/or HBGAs binding sites between the two strains. In summary, we determined the near-complete genome sequence of a GII.4 Sydney 2012 variant and produced an mAb with blocking effects that might be useful in evaluating the evolution of current Sydney 2012 NoV strains.

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Acknowledgements

This work was supported by the Provincial Joint Construction Program, Medical Science and Technology Research Program, Henan Province (Grant No. 2018020657).

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Authors and Affiliations

Authors

Contributions

YH and LG conceived and designed the experiments. LG, XC, JL, LZ, CC, SL, PG, and JK performed the experiments. LG, XC, JL analyzed the data. YH prepared the manuscript.

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Correspondence to Lili Ge or Yuqi Huo.

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The authors declare that they have no conflicts of interest.

Research involving human participants and/or animals

Animal experiments and mAb production were carried out at Wuhan NewEast Biosciences by following the guidelines of Chinese Council on Animal Care.

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Written informed consent for fecal sample was obtained from the father.

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Edited by Joachim Jakob Bugert.

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Ge, L., Chen, X., Liu, J. et al. Genomic and biological characterization of a pandemic norovirus variant GII.4 Sydney 2012. Virus Genes 56, 174–181 (2020). https://doi.org/10.1007/s11262-019-01729-0

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