Norovirus

Abstract

Norovirus infections are the leading cause of acute gastroenteritis globally. Despite the increasing recognition of norovirus infections in various animal species, there is to date no evidence of an animal reservoir for human norovirus, and transmission of norovirus is primarily person‐to‐person. Contaminated food, water and environment act as important amplifiers for infection. Human noroviruses are very diverse; however, one genotype GII‐4 predominates globally and is responsible for nearly half of all the infections and for a higher proportion of the outbreaks. Recently, in vitro systems for the propagation of human noroviruses have been developed, and there is an expectation that in the coming years, these will provide new insights into the molecular biology of human noroviruses and a better understanding of factors that determine susceptibility to and protection form infection. Host genetic factors and comorbidities in addition to potentially modifiable factors such as microbiome and use of certain treatment and drugs are increasingly recognised as important drivers of susceptibility to infection.

Key Concepts

  • Norovirus is the leading cause of acute gastroenteritis in humans.
  • Transmission of norovirus is predominantly person‐to‐person and is greatly amplified via contaminated food, water and environment.
  • Glycans act as attachment factors that mediate viral infection and cell entry and potentially drive host restriction.
  • New in vitro systems have recently been developed for human norovirus replication: B cell‐ and stem cell‐derived enteroids.
  • Virus diversity and host genetic and acquired factors are important drivers of susceptibility to infection.
  • The host microbiome has been recognised as an important factor for susceptibility to norovirus infection and clearance.

Keywords: norovirus; epidemiology; susceptibility; diversity

Figure 1. (A) A VP1 dimer, as found in the ‘AB’ conformation in the capsid of Norwalk virus. The VP1 protein is divided into two regions, the shell (S) (green highlighted region) found on the internal surface of the icosahedral virion and the protruding (P) domain that extends outwards and is thought to mediate attachment and entry into the host cell. The P domain can be further subdivided into P1 (red) and P2 (blue). The P2 domain contains the binding pocket for HBGA (a) (approximate position labelled). For clarity, the other VP1 protein in the dimer has been left unshaded – the dimer–dimer interface indicating the region of interaction. (B) The norovirus capsid has icosahedral symmetry (simplified diagram shown) with 180 copies of the VP1 protein forming the complex 3D structure. The capsids of norovirus are thought to dimerise in two conformations (A/B – shown earlier and C/C – not shown). These alternative dimers then assemble at points of five‐ (b) and three‐ (c) fold symmetry to allow sufficient curvature to close the capsid structure. An approximate example of the A/B dimer interactions at the fivefold axis of symmetry (b) is shown. For simplicity, the protruding domains have been removed from the crystal structures, and a top‐down view of 5 A/B dimer S domains is presented (again one half of the dimer has been left unshaded). Molecular graphics images were produced using the Chimera package from the Resource for Biocomputing, Visualization and Informatics at the University of California, San Francisco (supported by NIH P41 RR‐01081). The norovirus capsid structure was downloaded from the open access Research Collaboratory for Structural Bioinformatics (RCSB) protein data bank. PDB file reference: 1ihm, Prasad et al. 1999.
Figure 2. Schematic representation of the human norovirus genome with ORFs and encoded proteins.
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Iturriza‐Gómara, Miren, and Harris, John(Oct 2017) Norovirus. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0000420.pub2]