Canine distemper virus induces apoptosis in cervical tumor derived cell lines
Helen L Del Puerto1, Almir S Martins, Amy Milsted
1Department of General Pathology, Institute of Biological Science, Universidade Federal de Minas Gerais, UFMG, Brazil. helendelpuerto@hotmail.com
Abstract:
Apoptosis can be induced or inhibited by viral proteins, it can form part of the host defense against virus infection, or it can be a mechanism for viral spread to neighboring cells. Canine distemper virus (CDV) induces apoptotic cells in lymphoid tissues and in the cerebellum of dogs naturally infected. CDV also produces a cytopathologic effect, leading to apoptosis in Vero cells in tissue culture. We tested canine distemper virus, a member of the Paramyxoviridae family, for the ability to trigger apoptosis in HeLa cells, derived from cervical cancer cells resistant to apoptosis. To study the effect of CDV infection in HeLa cells, we examined apoptotic markers 24 h post infection (pi), by flow cytometry assay for DNA fragmentation, real-time PCR assay for caspase-3 and caspase-8 mRNA expression, and by caspase-3 and -8 immunocytochemistry. Flow cytometry showed that DNA fragmentation was induced in HeLa cells infected by CDV, and immunocytochemistry revealed a significant increase in the levels of the cleaved active form of caspase-3 protein, but did not show any difference in expression of caspase-8, indicating an intrinsic apoptotic pathway. Confirming this observation, expression of caspase-3 mRNA was higher in CDV infected HeLa cells than control cells; however, there was no statistically significant change in caspase-8 mRNA expression profile. Our data suggest that canine distemper virus induced apoptosis in HeLa cells, triggering apoptosis by the intrinsic pathway, with no participation of the initiator caspase -8 from the extrinsic pathway. In conclusion, the cellular stress caused by CDV infection of HeLa cells, leading to apoptosis, can be used as a tool in future research for cervical cancer treatment and control.
Insights
Canine distemper virus (CDV) triggers apoptosis in cervical cancer HeLa cells via the intrinsic pathway. This viral-induced cell death mechanism shows potential for future cervical cancer treatment strategies.
Area of Science:
- Virology
- Cell Biology
- Cancer Research
Background:
- Apoptosis plays a dual role in viral infections, acting as both a host defense and a viral spread mechanism.
- Canine distemper virus (CDV) is known to induce apoptosis in infected canine tissues and cell cultures.
- Cervical cancer cells, like HeLa cells, can be resistant to apoptosis.
Purpose of the Study:
- To investigate the capacity of canine distemper virus (CDV) to induce apoptosis in HeLa cells, a cervical cancer cell line resistant to programmed cell death.
- To elucidate the specific apoptotic pathway triggered by CDV infection in HeLa cells.
Main Methods:
- HeLa cells were infected with CDV.
- Apoptotic markers were assessed 24 hours post-infection using flow cytometry for DNA fragmentation.
- Real-time PCR and immunocytochemistry were employed to analyze the expression of caspase-3 and caspase-8.
Main Results:
- Flow cytometry confirmed DNA fragmentation in CDV-infected HeLa cells.
- Immunocytochemistry revealed increased levels of cleaved caspase-3, indicating activation of the intrinsic apoptotic pathway.
- Caspase-8 expression remained unchanged, suggesting the extrinsic pathway was not involved.
Conclusions:
- Canine distemper virus (CDV) effectively induces apoptosis in HeLa cervical cancer cells.
- The intrinsic apoptotic pathway, mediated by caspase-3, is activated by CDV infection in these cells.
- CDV-induced apoptosis in HeLa cells presents a potential avenue for future cervical cancer therapeutic research.
