SPHERICAL VIRUS STRUCTURES

$6,427P41FY2011RRNIH

Scripps Research Institute, The, La Jolla CA

Investigators

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Abstract

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. MNV is the first murine calcivirus structure and neutralization studies. Human caliciviruses are the major cause of epidemic gastroenteritis in adults, and thereby cause significant morbidity and economic loss. Important to human health, it is not known whether it is possible to effectively vaccinate against these agents, and mechanisms of vaccination are undefined. Thus, the lack of a small animal model with extensive genetic and immunologic tools for the analysis of pathogenesis and immunity has held back research on these important viruses. The H.W. Virgin laboratory has discovered the first murine calicivirus that they have designated Mouse Norovirus 1 or MNV-1. Unique amongst the Caliciviruses, they have developed both a whole animal and cell culture system. This affords new opportunities for basic research into calicivirus virology and immunology. Specifically, some of the questions we can address by analyzing the various structures of MNV-1: [unreadable] What are the important structural determinants that are recognized by antibodies that confer protection? [unreadable] What types of structural changes result in attenuation of the virus? [unreadable] Is the capsid dynamic and do neutralizing/protecting antibodies act by affecting these dynamics? [unreadable] Where does the receptor bind to the capsid and what are the determinants that dictate species specificity?

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