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Induction of cell death by adenoviruses
1Cell Transformation Group, Department of Pathology, School of Medicine, University of Otago, Box 913, Dunedin, New Zealand. antony.braithwaite@stonebow.otago.ac.nz
Abstract:
Adenoviruses have proved to be excellent tools for gaining insight into the regulation, and deregulation, of the mammalian cell cycle. With the widespread clinical use of gene therapy fast approaching, there comes a need for a better understanding of how the cell death process is regulated. A greater understanding will allow the development of therapeutic approaches that both maximise transgene expression while minimising cytotoxicity to the target cell. Consequently, much adenovirus research has centered on understanding the mechanisms governing adenovirus induced cell death or apoptosis. This review discusses recent advances in the field of adenovirus cell death regulation and evaluates the roles of implicated gene products and their respective data. The data suggest the existence of multiple virus gene products involved in cell death regulation and point towards several distinct, yet related, cell death pathways. A discussion of the shortcomings of current adenoviral research, along with a proposed model based upon the data is also given.
Insights
Adenoviruses are key to understanding cell cycle regulation and cell death. Research on adenovirus-induced apoptosis informs gene therapy by minimizing cytotoxicity and maximizing transgene expression.
Area of Science:
- Molecular biology
- Cell biology
- Virology
Background:
- Adenoviruses are valuable tools for studying mammalian cell cycle regulation and deregulation.
- Clinical applications of gene therapy necessitate a deeper understanding of cell death processes.
- Minimizing cytotoxicity while maximizing transgene expression is crucial for effective gene therapy.
Purpose of the Study:
- To review recent advances in adenovirus-mediated cell death regulation.
- To evaluate the roles of specific gene products in apoptosis.
- To explore distinct, yet related, cell death pathways induced by adenoviruses.
Main Methods:
- Literature review of recent advances in adenovirus research.
- Analysis of data on implicated gene products.
- Evaluation of existing models of adenovirus-induced cell death.
Main Results:
- Multiple adenovirus gene products are involved in regulating cell death.
- Evidence suggests the existence of several distinct but related cell death pathways.
- Current adenoviral research has identified several shortcomings.
Conclusions:
- Adenovirus research provides critical insights into cell death mechanisms.
- Understanding these mechanisms is vital for developing safer and more effective gene therapies.
- A proposed model based on current data offers a framework for future research.