The Dynamic Capsid Structures of the Noroviruses

Viruses. 2019 Mar 8;11(3):235. doi: 10.3390/v11030235.

Abstract

Noroviruses are responsible for almost a fifth of all cases of gastroenteritis worldwide. New strains evolve every 2⁻4 years by escaping herd immunity and cause worldwide epidemics. In the US alone, noroviruses are responsible for ~20 million cases and more than 70,000 hospitalizations of infected children, annually. Efforts towards a vaccine have been hindered by a lack of detailed structural information about antibody binding and the mechanisms of antibody escape. Caliciviruses have 180 copies of the major capsid protein (VP1; ~58 kDa), that is divided into the N-terminus (N), the shell (S) and C-terminal protruding (P) domains. The S domain forms a shell around the viral RNA genome, while the P domains dimerize to form protrusions on the capsid surface. The P domain is subdivided into P1 and P2 subdomains, with the latter containing the binding sites for cellular receptors and neutralizing antibodies. There is increasing evidence that these viruses are extremely dynamic and this flexibility is critical for viral replication. There are at least two modes of flexibility; the entire P domain relative to the shell and within the P domain itself. Here, the details and possible roles for this remarkable flexibility will be reviewed.

Keywords: antibody neutralization; caliciviruses; dynamics; viral receptors.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Antibodies, Neutralizing / immunology*
  • Antibodies, Viral / immunology*
  • Binding Sites, Antibody
  • Capsid / chemistry*
  • Capsid Proteins / chemistry*
  • Gastroenteritis / virology
  • Genome, Viral
  • Humans
  • Norovirus / chemistry*
  • Protein Conformation
  • Receptors, Virus / chemistry

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Capsid Proteins
  • Receptors, Virus