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 of FCoV and development of FIP. The majority of FIP cases are caused by FCoV type I; however, the receptor that the virus uses to enter cells, including macrophages, remains unknown and the proteases additionally responsible for viral activation also remains poorly defined. Here, we propose to investigate the interactions of FCoV that play a role in cell culture adaptation and virus isolation and infection. Based on our preliminary data, we hypothesize that FIPV type I enters cells, including macrophages, through the ACE2 receptor, as with SARS-CoV-2. Together, we propose that ACE2 and host proteases are key drivers of viral pathogenesis in FIP. This hypothesis forms the foundation of our specific aims.

In Aim 1, we will continue our work developing a reverse genetics system for feline coronavirus. We will focus on generating an infectious clone of FIPV-Black, using the cell lines that we have recently characterized. Having a reliable reverse genetics system for FCoVs will allow us to generate viruses with specific mutations in the spike glycoprotein and in other proteins and test the roles of these sequences in cell culture.

In Aim 2, we propose to investigate the role of feline ACE2 as a receptor for entry of FCoV through investigating fACE2 expression in cell lines and in tissues of naturally infected cats, along with knock-down studies of ACE2.