Caspase-3/-8/-9, Bax and Bcl-2 expression in the cerebellum, lymph nodes and leukocytes of dogs naturally infected with canine distemper virus

Abstract

ABSTRACT. Canine distemper is an immunosuppressive disease caused by the canine distemper virus (CDV). Pathogenesis mainly involves the central nervous system and immunosuppression. Dogs naturally infected with CDV develop apoptotic cells in lymphoid tissues and the cerebellum, but this apoptotic mechanism is not well characterized. To better understand this process, we evaluated the expression of Bax, Bcl-2, and caspase-3, -8 and -9, by evaluating mRNA levels in the peripheral blood, lymph nodes and cerebellum of CDV-infected (CDV+) and uninfected (CDV-) dogs by real-time polymerase chain reaction (PCR). Blood samples from 12 CDV+ and 8 CDV-dogs, diagnosed by reverse transcription-PCR, were subjected to hematological analysis and apoptotic gene expression was evaluated using real-time-PCR. Tissues from the cerebellum and lymph nodes of four CDV+ and three CDVdogs were also subjected to real time-PCR. No significant differences were found between CDV+ and CDV-dogs in the hemotological results or in the expression of caspase-3, -8, -9, Bax, and Bcl-2 in the peripheral blood. However, expression of Bax, caspase-3, -8 and -9 was significantly higher in the cerebellum of CDV+ compared to CDV-dogs. Expression of caspase-3 and -8 was significantly higher in the lymph nodes of CDV+ compared to CDV-dogs. We concluded that infection with CDV induces apoptosis in the cerebellum and lymph nodes in different ways. Lymph node apoptosis apparently occurs via caspase-3 activation, through the caspase-8 pathway, and cerebellum apoptosis apparently occurs via caspase-3 activation, through the caspase-8 and mitochondrial pathways.

Quantitative Analysis of Cellular Proteome Alterations in CDV-Infected Mink Lung Epithelial Cells

“…CTSK and CTSV are associated with a mitochondria-dependent intrinsic pathway to trigger the apoptosis of host cells, while TNF-a participates in an extrinsic receptor-mediated pathway (Benedict et al, 2002 ). This finding was consistent with previous reports showing that CDV induces apoptosis in the cerebellum and lymphoid tissues of the natural infection of dogs and in Vero cells in vitro (Moro et al, 2003 ; Del Puerto et al, 2010 , 2011 ). The mechanisms of apoptosis in the pathogenesis of CDV have not yet been clearly illuminated, and the extensive study of these proteins should enhance the current understanding of the mechanisms underlying apoptosis regulation during CDV infection.…”

BTG2: A rising star of tumor suppressors (Review)

“…BTG2 stimulates PRMT1 (protein arginine methyltransferase 1), promoting DNA repair of DSBs and Mre 11 methylation (27,40). In addition, BTG2 upregulates Bax gene to promote apoptosis (41).…”

Expression of Concern: Tumour necrosis factor‐alpha‐induced protein 8 (TNFAIP8) expression associated with cell survival and death in cancer cell lines infected with canine distemper virus

“…Both apoptosis induction and inhibition may be part of the host defense against virus infection, or they can be a mechanism for viral spread to neighboring cells . CDV has been shown to induce apoptosis in cerebellum and lymphoid tissue of naturally infected dogs, through the extrinsic pathway, activating caspase‐8 and caspase‐3 gene expression . In addition, CDV has been shown to induce apoptosis of Vero cells by triggering the extrinsic pathway, with caspase‐8 and caspase ‐3 activation .…”