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.

We are making a detailed examination of the interaction between FCV and its cell surface receptor, feline junctional adhesion molecule A (fJAM-A), experiments that are guided by a new atomic resolution structure of the FCV capsid. Using structural information, we are designing a panel of mutant viruses and receptors by recombinant DNA techniques. We plan to use this panel of mutants to interrogate which changes in the virus and in the receptor are critical for binding and infection.

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.