Region-Specific Apoptosis-Related Gene Expression Is Uncoupled from Viral RNA Load in Canine Distemper...

Canine distemper virus (CDV) is a highly contagious morbillivirus associated with severe neurological disease in dogs. Although apoptosis is recognized as an important mechanism in CDV-associated neurodegeneration, the relationship between regional viral RNA load and apoptosis-related transcriptional responses remains poorly defined. This study aimed to quantify CDV RNA load and the expression of apoptosis-related genes, including the pro-apoptotic markers Bax, caspase-3 and caspase-8 and the anti-apoptotic marker Bcl-2, in the frontal cortex, hippocampus, and cerebellum of 21 dogs naturally infected with CDV, compared with four neurologically normal controls. Viral RNA load and gene expression were assessed by quantitative reverse transcription PCR (qRT-PCR). CDV RNA was detected in all brain regions of infected dogs, with no significant differences in viral RNA load among the frontal cortex, hippocampus and cerebellum (p > 0.05). In contrast, apoptosis-related gene expression showed a region-specific pattern. In the hippocampus, Bax (2.56-fold, p < 0.05), caspase-8 (4.33-fold, p < 0.05) and caspase-3 (2.01-fold, p < 0.05) were significantly upregulated in CDV-infected dogs compared with controls. In the cerebellum, Bax (2.07-fold, p < 0.05) and caspase-3 (1.97-fold, p < 0.05) were also increased, whereas no significant differences were observed in any apoptotic marker in the frontal cortex. Pearson correlation analysis revealed no significant association between regional viral RNA load and expression of Bcl-2, Bax, caspase-3 or caspase-8 in any of the brain regions examined. These findings suggest that CDV-associated apoptosis-related transcriptional responses in the central nervous system are region-dependent and are not linearly associated with local viral RNA load. This study provides new insights into the heterogeneous neuropathogenesis of CDV and supports the importance of regional brain susceptibility in viral encephalitis.