Contact Information: Email: firstname.lastname@example.org; Phone: 607-253-4019
Sponsor: Morris Animal Foundation
Grant Number: D10FE-511
Title: Host and Viral Determinants of FIP Pathogenesis: Toward a Diagnostic Tool for Shelter Cat Management
Annual Direct Cost: $56,296
Project Period: 07/01/11-06/30/13
DESCRIPTION (provided by applicant): FIP is a fatal, progressive, and immune-augmented disease of cats caused by infection by a feline coronavirus (FCoV). It is commonly considered to be the most significant infectious disease in feline medicine, especially in shelter situations, occurring most frequently in cats less than two years of age or, less commonly, in geriatric cats. FCoVs exist in both nonpathogenic (FECV) and pathogenic (FIPV) forms, but viral or host genetic determinants specifically associated with FIPV pathogenesis have yet to be discovered. Our preliminary sequencing studies have recently determined that a processing site for an activating protease is present on the spike protein of FECVs, which is mutated in cats with FIP. Our hypothesis is that modification of the processing site correlates with the conversion of FECV to FIPV, and causes a change in the entry pathway of the virus, allowing escape of the virus from gut epithelial cells and into monocytes and macrophages. We will test the universality of this hypothesis by extending our current sequencing studies of FECVs and FIPV, using a diverse set of geographically and temporally distinct FCoVs. We have also shown a critical role for C-type lectins on host immune cells in virus entry and disease progression. It is known that there is heterogeneity in C-type lectin expression in other species, suggesting this as a genetic factor in the progression of FIP in individual cats or within distinct breeds. To test this hypothesis, we propose a cohort analysis of C-type lectin expression in FIPV cases versus FECV asymptomatic controls from a geographically distinct population. Overall, we believe our work will fundamentally change our view of feline coronavirus infection, shed significant light onto the process of viral pathogenesis and lead to desperately needed diagnostic tools for shelter cat management.