Structural studies on gastroenteritis viruses

Novartis Found Symp. 2001:238:26-37; discussion 37-46. doi: 10.1002/0470846534.ch3.

Abstract

There are many recent advances in our understanding of the structure-function relationships in rotavirus, a major pathogen of infantile gastroenteritis, and Norwalk virus, a causative agent of epidemic gastroenteritis in humans. Rotavirus is a large (1000 A) and complex icosahedral assembly formed by three concentric capsid layers that enclose the viral genome of 11 dsRNA segments. Because of its medical relevance, intriguing structural complexity, and several unique strategies in the morphogenesis and replication, this virus has been the subject of extensive biochemical, genetic and structural studies. Using a combination of electron cryomicroscopy and computer image processing together with atomic resolution X-ray structural information, we have been able to provide not only a better description of the rotavirus architecture, but also a better understanding of the structural basis of various biological functions such as trypsin-enhanced infectivity, virus assembly and the dynamic process of endogenous transcription. In contrast to rotavirus, Norwalk virus has a simple architecture with an icosahedral capsid made of 180 copies of a single protein. We have determined the structure of the Norwalk virus capsid to a resolution of 3.4 A using X-ray crystallographic techniques. These studies have provided valuable information on domain organization in the capsid protein, and residues that may be critical for dimerization, assembly, strain-specificity and antigenicity.

Publication types

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

MeSH terms

  • Capsid / chemistry*
  • Capsid / ultrastructure
  • Gastroenteritis / virology*
  • Gene Expression Regulation, Viral
  • Humans
  • Molecular Conformation
  • Norwalk virus / chemistry*
  • Norwalk virus / ultrastructure
  • RNA, Viral / metabolism
  • Rotavirus / chemistry*
  • Rotavirus / genetics
  • Rotavirus / metabolism
  • Rotavirus / ultrastructure
  • Trypsin / metabolism

Substances

  • RNA, Viral
  • Trypsin