Principal Investigator: Gary Whittaker

DESCRIPTION (provided by applicant): 

Feline infectious peritonitis is a leading cause of mortality in pet cats worldwide, caused by feline coronavirus (FCoV). Internal mutation of the virus is believed to drive macrophage tropism. However, the receptor that the virus uses to enter the macrophage remains unknown and the protease responsible for viral activation in macrophages also remains unidentified. Moreover, the interaction of the virus with metabolic pathways of the macrophage has also not been explored. Here, we propose to investigate the interactions of FCoV that may play a role in macrophage tropism, viral activation, and systemic disease. In aim 1, we propose to investigate the role of the macrophage marker CD163 as a receptor for macrophage entry of FCoV through investigating CD163 expression in cell lines and in tissues of naturally infected cats. In aim 2, we will determine the role of the protease, plasmin, as an FIPV activator, through in vitro studies utilizing cell culture lines which express plasmin and in vivo studies of plasmin activity and D-dimer quantification. Lastly, in aim 3, we will investigate viral interaction with macrophage metabolic pathways, focusing on the four isoforms of pyruvate kinase through genotypic expression, a pyruvate activity assay and co-immunoprecipitation. Together these aims will provide insight into FIPV mechanisms which may be driving macrophage tropism and systemic disease.