Genome-wide analyses of human noroviruses provide insights on evolutionary dynamics and evidence of coexisting viral populations evolving under recombination constraints

PLoS Pathog. 2021 Jul 13;17(7):e1009744. doi: 10.1371/journal.ppat.1009744. eCollection 2021 Jul.

Abstract

Norovirus is a major cause of acute gastroenteritis worldwide. Over 30 different genotypes, mostly from genogroup I (GI) and II (GII), have been shown to infect humans. Despite three decades of genome sequencing, our understanding of the role of genomic diversification across continents and time is incomplete. To close the spatiotemporal gap of genomic information of human noroviruses, we conducted a large-scale genome-wide analyses that included the nearly full-length sequencing of 281 archival viruses circulating since the 1970s in over 10 countries from four continents, with a major emphasis on norovirus genotypes that are currently underrepresented in public genome databases. We provided new genome information for 24 distinct genotypes, including the oldest genome information from 12 norovirus genotypes. Analyses of this new genomic information, together with those publicly available, showed that (i) noroviruses evolve at similar rates across genomic regions and genotypes; (ii) emerging viruses evolved from transiently-circulating intermediate viruses; (iii) diversifying selection on the VP1 protein was recorded in genotypes with multiple variants; (iv) non-structural proteins showed a similar branching on their phylogenetic trees; and (v) contrary to the current understanding, there are restrictions on the ability to recombine different genomic regions, which results in co-circulating populations of viruses evolving independently in human communities. This study provides a comprehensive genetic analysis of diverse norovirus genotypes and the role of non-structural proteins on viral diversification, shedding new light on the mechanisms of norovirus evolution and transmission.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Biological Evolution
  • Evolution, Molecular
  • Genome, Viral / genetics*
  • Genome-Wide Association Study
  • Humans
  • Norovirus / genetics*

Grants and funding

This work was funded by the Center for Biologics Evaluation and Research (CBER), Food and Drug Administration (FDA), DHHS to G.I.P. Partial funding was also provided by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health to K.Y.G. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.