Structural studies on gastroenteritis viruses

B. V. Venkataram Prasad*, S. Crawfordf, J. A. Lawton*1, J. Pesavento*, M. Hardyf2, and M. K. Estesf

* Verna and Maars McLean Department of Biochemistry and Molecular Biology, and f Department of Molecular Virology and Microbiology, Baylor College of Medicine, One Baylor Pla^a, Houston, TX 77030, USA

A bstract. 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.

2001 Gastroenteritis viruses. Wiley, Chichester (Novartis Foundation Symposium 238) p 26-46

In recent years electron cryoelectron microscopy coupled with computer image processing (cryo-EM), and X-ray crystallography have provided valuable structural information on gastroenteritis viruses such as rotavirus and Norwalk virus. These studies have provided further insights into the intricate molecular

Present addresses: department of Chemistry and Biochemistry, 0314, University of California at San Diego, 9500 Gilman Drive, San Diego, CA 92093, USA and 2Veterinary Molecular Biology, Montana State Univ., Bozeman, MT 59717, USA

mechanisms underlying various aspects of the viral life cycle. Here we review recent progress in the structural characterization of these two viruses.

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