Pathological alteration and caspase-dependent activity of feline kidneys in natural infection of feline morbillivirus.

Background: Feline morbillivirus (FeMV) has been associated with renal pathology in cats; however, the specific pathological alterations caused by FeMV infection remain controversial. This study aimed to investigate histopathological changes, viral localization, and apoptotic activity in the kidneys of FeMV-infected cats.

Methods: Kidney tissues from 150 deceased cats with suspected or confirmed chronic kidney disease (CKD) were screened for FeMV using conventional reverse-transcription PCR (cRT-PCR). Positive cases were genotyped and quantified for viral load using reverse-transcription digital PCR (RT-dPCR). A control group of nine FeMV-negative kidneys with CKD was included for comparison. Histological evaluation was conducted using hematoxylin and eosin (H&E), periodic acid-Schiff (PAS), and Masson's trichrome staining. Immunohistochemistry (IHC) and in situ hybridization (ISH) were employed to localize viral antigens and assess expression of apoptotic markers, including cleaved caspase-3 (cCasp3), B-cell lymphoma 2 (BCL-2), and BCL-2-associated X protein (BAX).

Results: FeMV RNA was detected in 6% (9/150) of kidneys, all classified as genotype 1. Histological findings in FeMV-positive cases included eosinophilic intracytoplasmic inclusion bodies, lymphoplasmacytic tubulointerstitial nephritis (TIN) and varying degrees of fibrosis. FeMV antigens were localized in the renal tubular epithelial cells. Statistically, cCasp3 expression (P = 0.005) and interstitial fibrosis (P = 0.040) were significantly higher in FeMV-positive cases than in FeMV-negative controls. No significant differences were observed for TIN, BAX, or BCL-2 expression (P > 0.05). Among FeMV-positive cases, viral load was significantly associated with cCasp3 expression (P = 0.049), but not with TIN, fibrosis, BAX, or BCL-2 expression. Spearman's correlation revealed a strong positive correlation between viral load and cCasp3 expression (ρ = 0.8222, P = 0.007).

Conclusions: FeMV infection in cats was associated with increased caspase-3-mediated apoptotic activity and interstitial fibrosis in kidney tissue, particularly in cases with higher viral loads. While these findings suggest a possible role for FeMV in renal injury, the absence of consistent associations with other apoptotic markers and inflammatory parameters indicates that additional factors may contribute to disease progression. Further studies, including longitudinal and experimental investigations, are needed to clarify the pathogenic mechanisms and the clinical relevance of FeMV in feline kidney disease.