Submitted to: American Society for Virology Meeting
Publication Type: Abstract only
Publication Acceptance Date: 7/12/2003
Publication Date: 7/12/2003
Citation: Chen, R., Neill, J.D., Noel, J.S., Huston, A.M., Glass, R.I., Estes, M.K., Prasad, B.V. Analysis of intra genus and inter genera structural variations in the members of caliciviridae. American Society for Virology Meeting. 2003. p. 229. Abstract No. P19-6. Interpretive Summary:
Technical Abstract: Caliciviruses, members of the Caliciviridae, are non-enveloped icosahedral T=3 viruses with the capsid mainly composed of a single capsid protein VP1. The Caliciviridae is divided into four genera: Norovirus, Sapovirus, Lagovirus and Vesivirus. Noroviruses and sapoviruses are mainly human pathogens, whereas lagoviruses and vesiviruses are exclusively animal pathogens. Human caliciviruses are the major cause of outbreaks of non-bacterial gastroenteritis, where animal caliciviruses cause a wide range of host-dependent diseases. To investigate the structural basis of host specificity and strain diversity, we have carried out comparative cryo-EM structural studies on representative caliciviruses from three different genera: recombinant Norwalk virus (genotype 1, Norovirus capsid), recombinant Grimsby virus (genotype 2, Norovirus capsid), recombinant Parkville virus (Sapovirus capsid) and San Miguel sea lion virus serotype 4 (SMSV4, Vesivirus). Our structural analysis indicated that the capsid protein of all these caliciviruses mainly folds into two domains - shell (S) and protrusion (P), and the P domain is further divided into two sub-domains. The most external P2 sub-domain, also the most sequence variable region, exhibits significant structural differences among these caliciviruses, suggesting that it may have determinants for host specificity and strain diversity. The P1 sub-domain, although oriented differently with respect to the S domain in different viruses, appears to be structurally conserved. Structural comparison showed that the recombinant Parkville virus capsid is structurally more similar to animal caliciviruses. In addition, we have crystallized SMSV4 and collected a complete diffraction data set to 3.2 Å resolution from a frozen crystal. Structural determination is in progress and the structure of this intact calicivirus will provide more insights into the structure-function relationship in caliciviruses.