Complement Evasion Protects FCoV from Virus Clearance Within Prototypic FIP Lesions

Area of Science:

• Veterinary Immunology
• Feline Infectious Diseases
• Complement System Biology

Background:

• Feline infectious peritonitis (FIP) is a fatal disease caused by feline coronavirus (FCoV).
• The feline immune system, including the complement system, fails to clear FCoV during FIP.
• Mechanisms of complement system inefficacy during FIP pathogenesis remain unclear.

Purpose of the Study:

• To investigate the role of complement-regulating factors (CRFs) in FIP pathogenesis.
• To determine the spatial expression of CD46 and CD59 in FIP lesions.
• To assess the relationship between CRFs, complement activation (C1q, C9), and FCoV-infected cells.

Main Methods:

• Multiplex immunohistochemistry was used to analyze archived tissue samples from 31 cats with FIP.
• Spatial expression of CD46, CD59, C1q, and C9 was evaluated in FIP lesions.
• Colocalization with FCoV-infected cells and proximity to lesions were assessed.

Main Results:

• FIP lesions showed marked expression of CD46 and CD59 near FCoV-infected macrophages.
• CRF expression was significantly lower in FIP lesions compared to areas distal to FCoV-infected cells.
• Complement-activating factors C1q and C9 expression was higher in FIP lesions.

Conclusions:

• FCoV-infected macrophages in cats with FIP utilize autocrine and paracrine expression of CRFs.
• CRFs shield FCoV-infected macrophages from complement-mediated destruction.
• This immune evasion strategy contributes to the pathogenesis of FIP.