Advancing the health and well-being of animals and people


Principal Investigator:  John Parker

Contact Information: Email: jsp7@cornell.edu; Phone: 607-256-5626
Sponsor: Morris Animal Foundation
Grant Number: D12FE-002
Title: The Role of Feline Junctional Adhesion Molecule A in Feline Calcivirus (FCV) Infection
Annual Direct Cost: $69,675
Project Period: 09/1/2011- 08/31/2014

DESCRIPTION (provided by applicant): Feline calicivirus (FCV) is a common cause of upper respiratory disease and oral ulceration in cats. Of concern are reports of severe and sometimes-fatal virulent systemic disease caused by FCV. Isolates recovered from cats with virulent systemic (VS)-FCV have reproduced the disease indicating that the virus and not some other factor is responsible for this new disease. Here we propose to examine in detail the interaction between FCV and its cell surface receptor, feline Junctional adhesion molecule A (fJAM-A). Our experiments will be guided by a new atomic resolution structure of the FCV capsid. The approach we will take will be to use structural information to design a panel of mutant viruses and receptors by recombinant DNA techniques. We will then use this panel of mutants to ask which changes in the virus and in the receptor are critical for binding and infection. The rationale for these experiments is that based on our preliminary findings we strongly suspect that newer virulent isolates of FCV undergo dramatic conformational changes upon interaction with fJAM-A that make these viruses more efficient at infecting cells. An increase in infection efficiency within an animal could over the course of multiple rounds of infection lead to enhanced virulence and pathogenicity. The benefit of obtaining this information is that we expect to identify critical residues in the FCV capsid that are predictors of this behavior and thus allow potential VS-FCV isolates to be identified early. Secondly, by understanding the molecular mechanisms by which these viruses infect cells, we can better design therapies and potentially engineer vaccine candidates. One potential therapy might be to use soluble forms of the receptor itself to neutralize the virus.