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Principal Investigator: Gary Whittaker
Contact Information: E-mail: grw7@cornell.edu - Phone: 607-253-4019
Sponsor: Winn Feline Foundation
Grant Number: W 08-0004
Title: Molecular Basis of Feline Coronavirus Pathogenesis and Development of FIP in Cats
Annual Direct Cost: $15,000
Project Period: 03/01/08-02/28/09
DESCRIPTION (provided by applicant): Feline infectious peritonitis (FIP) is a lethal systemic infection in cats, caused by feline coronavirus (FCoV). Infection by FCoV normally causes a mild and often inapparent enteritis, in which case the virus is referred to as feline enteric coronavirus (FECV). In the “internal mutation” model of FIP, it is believed that a process of mutation within an individual cat confers the ability of FECV to infect macrophages, and so become feline infectious peritonitis virus (FIPV)—the virus that causes FIP. However there has been little experimental support to date for the internal mutation theory of FIPV. Here we hypothesize that that mutation of the FECV spike protein results in changes in the processing of the spike protein by host cell proteases, which leads to acquisition of a hyper-fusogenic spike protein and confers the ability of the virus to infect macrophages—and so initiate the process of FIP. We will test this hypothesis by cloning the spike proteins or a range of feline coronaviruses, and performing site-directed mutagenesis followed by direct fusion assays, and incorporation of wild type and mutant spike proteins in pseudovirions. Fusion and entry will be monitored in feline epithelial cells and monocytes/macrophages in the presence of inhibitors proteases and endosomal pH, with the goal of determining the molecular changes that account for the acquisition of an FIP phenotype by the virus.
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