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Host Cell Interactions with Human Infectious Diseases, Straub


EMSL Project ID
16297a

Abstract

Pathogenesis is a complex biological process between the human host and the infectious disease agent. In our previous successful collaboration with EMSL scientists (EMSL Project 16297), which lead to a high impact publication in CDCs journal Emerging and Infectious Diseases, we began to unlock the mechanisms of the poorly understood gastrointestinal pathogen Norovirus. Unique 3-D cell culture systems developed by EMSL users allowed, for the first time, the ability to cultivate this pathogen in vitro. TEM imaging revealed that the interaction of the norovirus capsid proteins with their host cells caused significant internal eukaryotic cell membrane rearrangement. Proteomic analysis revealed unique, but as yet, uncharacterized host secreted peptides in response to norovirus challenge. This proposal will seek to understand the biological interactions of viral and host proteins. Understanding these processes will enhance our understanding of infectious diseases and lead to unique opportunities for development of rapid diagnostics, vaccines and therapeutics.

Project Details

Project type
Large-Scale EMSL Research
Start Date
2007-05-29
End Date
2010-09-30
Status
Closed

Team

Principal Investigator

Timothy Straub
Institution
Pacific Northwest National Laboratory

Team Members

Patricia Orosz Coglhan
Institution
University of Arizona

Rachel Bartholomew
Institution
Pacific Northwest National Laboratory

Catherine Valdez
Institution
Pacific Northwest National Laboratory

Jan Vinje
Institution
Centers for Disease Control and Prevention

Shay Fout
Institution
United States Environmental Protection Agency

Kerstin Honer Zu Bentrup
Institution
Tulane University

Charles Gerba
Institution
University of Arizona

Cheryl Nickerson
Institution
Arizona State University

Cindy Bruckner-Lea
Institution
Pacific Northwest National Laboratory

Alice Dohnalkova
Institution
Environmental Molecular Sciences Laboratory

Bruce Arey
Institution
Pacific Northwest National Laboratory

Related Publications

Straub TM, Bartholomew RA, Valdez CO, Valentine NB, Dohnalkova A, Ozanich RM, Bruckner-Lea CJ, Call DR. 2010. Human norovirus infection of Caco-2 cells grown as a three dimensional tissue structure. Journal of Water and Health. in press. doi: 10.2166/wh.2010.106
Straub TM, Honer zu Bentrup K, Orosz-Coghlan P, Dohnalkova A, Mayer BK, Bartholomew RA, Valdez CO, Bruckner-Lea CJ, Gerba CP, Abbaszadegan M, Nickerson CA. 2007. In vitro cell culture infectivity assay for human noroviruses. Emerg Infect Dis. 13(3) 396-403.
Straub TM, RA Bartholomew, CO Valdez, NB Valentine, A Dohnalkova, RM Ozanich, CJ Bruckner-Lea, and DR Call. 2011. "Human Norovirus Infection of Caco-2 Cells Grown as a Three-Dimensional Tissue Structure." Journal of Water and Health 9(2):225-240.