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Vaccinia virus evasion of regulated cell death
David L Veyer1, Guia Carrara2, Carlos Maluquer de Motes3
1Laboratoire de Virologie, Hôpital Européen Georges Pompidou, 20 Rue Leblanc, 75015 Paris, France.
Abstract:
Regulated cell death is a powerful anti-viral mechanism capable of aborting the virus replicative cycle and alerting neighbouring cells to the threat of infection. The biological importance of regulated cell death is illustrated by the rich repertoire of host signalling cascades causing cell death and by the multiple strategies exhibited by viruses to block death signal transduction and preserve cell viability. Vaccinia virus (VACV), a poxvirus and the vaccine used to eradicate smallpox, encodes multiple proteins that interfere with apoptotic, necroptotic and pyroptotic signalling. Here the current knowledge on cell death pathways and how VACV proteins interact with them is reviewed. Studying the mechanisms evolved by VACV to counteract host programmed cell death has implications for its successful use as a vector for vaccination and as an oncolytic agent against cancer.
Insights
Regulated cell death is a key antiviral defense. Vaccinia virus (VACV) proteins block these cell death pathways, impacting its use in vaccines and cancer therapy.
Area of Science:
- Virology
- Immunology
- Cell Biology
Background:
- Regulated cell death is a critical host defense against viral infections, terminating viral replication and signaling to neighboring cells.
- Viruses have evolved diverse mechanisms to evade host-induced cell death and ensure their survival.
- Vaccinia virus (VACV), a poxvirus, encodes multiple proteins that actively interfere with host cell death pathways.
Purpose of the Study:
- To review current knowledge of regulated cell death pathways.
- To elucidate the mechanisms by which VACV proteins interact with and inhibit these cell death pathways.
- To discuss the implications of VACV's anti-death strategies for its applications in vaccination and oncology.
Main Methods:
- Literature review of existing research on regulated cell death and VACV.
- Analysis of VACV protein functions in relation to host cell death signaling cascades (apoptosis, necroptosis, pyroptosis).
- Synthesis of information on VACV's strategies to subvert host cell death.
Main Results:
- VACV encodes multiple proteins that target and inhibit key components of apoptotic, necroptotic, and pyroptotic pathways.
- VACV's interference with cell death is essential for successful viral replication within the host.
- Understanding these viral countermeasures provides insights into host-pathogen interactions.
Conclusions:
- VACV employs sophisticated strategies to counteract host-mediated regulated cell death.
- Knowledge of VACV's manipulation of cell death pathways is crucial for optimizing its use as a vaccine vector.
- VACV's ability to inhibit cell death pathways has potential therapeutic applications in cancer treatment as an oncolytic agent.