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  • Review Article
  • Published:

Human norovirus transmission and evolution in a changing world

Nature Reviews Microbiology volume 14, pages 421–433 (2016)Cite this article

Subjects

Key Points

  • Norovirus infections pose a substantial risk to human health worldwide. Modes of viral transmission, the severity of illness and evolutionary pressures all contribute to this risk and can vary between viral genotypes.

  • Many details about the transmission of noroviruses remain unknown, especially regarding the origin of newly emerging strains.

  • The recent emergence of genotype GII.P17-GII.17 noroviruses in Asia should serve as a warning that future risks from norovirus outbreaks might arise from genotypes other than those currently targeted by vaccine development.

  • Bacteria in the host microbiota might influence human norovirus infections by providing HBGA-like sugars for norovirus attachment and by modulating host immunity.

  • B cells support norovirus replication in the presence of bacteria that express histo-blood group antigen (HBGA)-like sugars. A recently described cell culture system for the study of noroviruses in B cells will hopefully advance our understanding of many aspects of human noroviruses, ranging from the molecular characterization of their life cycle to the development of improved vaccines.

Abstract

Norovirus infections are a major cause of gastroenteritis, and outbreaks occur frequently. Several factors are currently increasing the challenge posed by norovirus infections to global health, notably the increasing number of infections in immunocompromised individuals, who are more susceptible to disease, and the globalization of the food industry, which enables large norovirus outbreaks to occur on an international scale. Furthermore, the rapid rate of the genetic and antigenic evolution of circulating noroviruses complicates the development of vaccines and therapies that are required to counter these challenges. In this Review, we describe recent advances in the study of the transmission, pathogenesis and evolution of human noroviruses, and consider the ongoing risk of norovirus outbreaks, together with the future prospects for therapeutics, in a rapidly changing world.

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Figure 1: The composition and life cycle of human noroviruses.
Figure 2: Norovirus epidemiology in the community.
Figure 3: Synthesis of histo-blood group antigens.
Figure 4: ORF1 and ORF2 phylogenies.
Figure 5: Mechanisms of norovirus evolution.

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Acknowledgements

This work was supported by the European Union's Horizon 2020 grant to the COMPARE Consortium, under grant agreement number 643476, and by the Virgo Consortium, funded by the Dutch Government (project number FES0908). The authors thank J. Le Pendu for helpful comments.

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Authors and Affiliations

  1. Department of Viroscience, Erasmus University Medical Center, P.O. Box 2040, Rotterdam, 3000CA, The Netherlands

    Miranda de Graaf, Janko van Beek & Marion P. G. Koopmans

Authors
  1. Miranda de Graaf
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  2. Janko van Beek
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  3. Marion P. G. Koopmans
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Corresponding author

Correspondence to Marion P. G. Koopmans.

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Glossary

Genogroups

Groups of related viruses within a genus.

Polyprotein

A large protein that is cleaved into separate smaller proteins with different biological functions.

Nosocomial transmission

The transmission of an infectious disease in a hospital setting.

Herd immunity

General immunity of a host population to a pathogen, mediated by immunity acquired by a high proportion of individuals within the population.

Gnotobiotic

Pertaining to an animal: germ-free, or having known associated microorganisms.

Lewis blood group

A blood group system based on the expression of glycoproteins called Lewis antigens.

Mesoamerican

From a region that extends south and east from central Mexico to include parts of Guatemala, Belize, Honduras and Nicaragua.

Villous blunting

Flattening of the intestinal villi as a result of damage or injury.

Host cell tropism

The specificity of a virus for a particular host cell type.

Virus-like particles

(VLPs). Particles that resemble natural viral particles and contain viral structural proteins, such as the envelope or capsid protein, but do not contain genetic material from the virus.

Goblet cells

Specialized epithelial cells that secrete mucus and are found in the mucous membranes of the stomach, intestines and respiratory passages.

Lamina propria

The layer of connective tissue that underlies the epithelium of a mucous membrane.

Brunner's glands

Tubular submucosal glands found in the duodenum.

DC-SIGN

(Dendritic-cell-specific ICAM3-grabbing non-integrin). A C-type lectin receptor present on the surface of macrophages and dendritic cells.

Interferon

One of several signalling proteins that are crucial components of the innate immune response to viral infection. Many viruses have proteins that block or modulate interferons.

Phylodynamic reconstruction

The reconstruction of epidemiological, immunological and evolutionary processes based on analyses of viral phylogenies.

Genetic drift

The change in the genetic composition of a population that occurs by chance or random events rather than by natural selection.

Replicon systems

Systems in which an incomplete viral genome is capable of autonomous replication.

Heterologous cross-protection

Protection conferred on a host by inoculation with one strain of a microorganism (or a component of the strain) that prevents infection when the host is later challenged with a different strain.

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de Graaf, M., van Beek, J. & Koopmans, M. Human norovirus transmission and evolution in a changing world. Nat Rev Microbiol 14, 421–433 (2016). https://doi.org/10.1038/nrmicro.2016.48

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