|
Principal Investigator: John Parker
Contact Information: E-mail: jsp7@cornell.edu - Phone: 607-256-5626
Sponsor: Winn Feline Foundation
Grant Number: 2007-35600-18539
Title: Are Differences in Feline Calicivirus (FCV) Tissue Tropism and Virulence Determined by changes in Virus Interactions with Cell Surface Glycans?
Annual Direct Cost: $15,750
Project Period: 01/01/08-12/31/08
DESCRIPTION (provided by applicant): New isolates of feline calicivims (FCV) cause severe life-threatening virulent systemic (VS) disease (3, 12, 17). VS-FCV isolates differ from non-VS isolates in their tissue and cell tropism, infecting epithelial and endothelial cells in several different organs (12, 13). Expanded cell and tissue tropism is often a consequence of changes in virus-receptor interactions (1, 2, 4, 6, 16, 20-22). We have shown that VS-FCV isolates spread more rapidly in tissue culture than non-VS FCV isolates (10). Our long term goals are to understand the relationship between FCV-receptor interactions and viral tropism, and to identify what role these interactions play in FCV virulence. Our central hypothesis is that increased rate of spread in tissue culture and altered tropism of VS-FCV isolates are partly determined by specific virus-receptor interactions. Recently, two cell surface molecules were identified as receptors for FCV - feline junctional adhesion molecule (7) and α2,6-1inked sialic acid (19). Glycans (carbohydrates e.g., sialic acid) are common receptor molecules for viruses and are often major determinants of tropism (18). The goals of this proposal are to determine the role that glycans play in determining the cell tropism of different FCV isolates and to identify the range of different glycans that FCV isolates can bind. We expect one outcome of these studies will be greater understanding of the role of glycans in FCV tropism and virulence. Studies of the basic biology of FCV are essential for rational development of new methods of diagnosis, treatment and prevention of FCV disease.
|
