2015 RESEARCH GRANT UPDATE

Gary Whittaker, PhD

Role of matrix metalloproteases in FIPV-infected macrophages and the development of FIP in cats

Gary Whittaker, PhD

The coronavirus that causes feline infectious peritonitis (FIP) starts out as a harmless hitchhiker in the cat’s intestinal tract, but if the virus enters the blood stream things can go terribly wrong. In these cases, coronavirus in the blood takes hold in the body’s macrophages, specialized cells of the immune system that are meant to attack invading pathogens. This triggers the macrophages to over respond to infection, starting the cat’s body on a downward spiral of inflammation, fever, weight loss, lethargy, and eventually death.

Dr. Gary Whittaker is trying to figure out how the virus makes the switch from harmless to lethal by gaining entry into macrophages. They’re focused on proteases in cat cells (enzymes that act like switches for many processes in the cell) that are known to activate the virus, and which differ between intestinal cells and macrophages. Whittaker has two main candidates for the elusive protease in macrophages: matrix metalloprotease (MMP) and proprotein convertase 1 (PC1). The work is complicated by the fact that the coronavirus seems to find many different solutions to the problem of entering different cell types, so Whittaker may have to explore many avenues to get a full picture. In the end, Whittaker and his team hope to learn about how the virus switches from harmless to lethal so they can identify existing drugs or design new drugs to inhibit that switchover.

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