Feline Coronavirus Infection: Implications For The Treatment Of Feline Infectious Peritonitis
Feline infectious peritonitis (FIP) is an untreatable and terminal disease of cats caused by systemic infection with a feline coronavirus termed feline infectious peritonitis virus (FIPV). This thesis investigates the cellular entry of FIPV in order to discover targets which may be of therapeutic value in treating this disease. This thesis demonstrates that FIPV utilizes the lectin DC-SIGN to enhance cellular uptake. This is significant because macrophages and dendritic cells, which express DC-SIGN at high levels, are infected by FIPV to initiate the disease process. This thesis also shows that FIPV activates the p38 MAPK signaling pathway in infected cells, and that this induces the overproduction of pro-inflammatory cytokines observed in cats with FIP. Finally this thesis demonstrates that feline coronaviruses require cathepsin cysteine proteases during entry to cleave and activate the viral spike protein. In addition, specific proteases are preferred over others depending on the pathogenicity of the virus. It is also shown that certain molecular inhibitors of cysteine proteases can block viral infection in primary feline cells, presumably by preventing cleavage of the spike protein during viral entry. These data highlight new therapeutic strategies for the treatment of FIP which will be discussed in the conclusion.
dissertation or thesis