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Innate immunity to adenovirus: lessons from mice
Svetlana Atasheva1, Jia Yao1, Dmitry M Shayakhmetov1,2,3
1Lowance Center for Human Immunology, Departments of Pediatrics and Medicine, Emory University School of Medicine, Atlanta, GA, USA.
FEBS Letters
|November 27, 2019
Summary
Adenovirus vectors can trigger dangerous immune responses in humans, but mouse studies reveal how the innate immune system detects and responds to these viruses, aiding in the development of safer gene therapies.
Area of Science:
- Immunology
- Virology
- Gene Therapy
Background:
- Adenoviruses are widespread pathogens with diverse hosts.
- While natural infections are mild, high-dose adenovirus vectors cause severe immune reactions like cytokine storm syndrome.
- Mouse models are crucial for understanding adenovirus-innate immunity interactions.
Purpose of the Study:
- To elucidate the mechanisms by which adenovirus activates the innate immune system.
- To identify cellular and molecular components involved in adenovirus detection and immune response.
- To inform the design of safer adenovirus-based vectors for therapeutic applications.
Main Methods:
- Intravenous administration of adenovirus to mouse models.
- Analysis of innate immune cell activation and cytokine production.
- Investigation of adenovirus clearance and infected cell elimination mechanisms.
Main Results:
- Adenovirus triggers rapid innate immune activation, including pro-inflammatory signaling and cytokine release.
- Specific cellular and molecular components were identified that detect adenovirus particles.
- Mechanisms for sequestering adenovirus from the bloodstream and eliminating infected cells were revealed.
Conclusions:
- Mouse studies provide critical insights into adenovirus-induced innate immunity.
- Understanding these mechanisms is key to developing safer adenovirus vectors for human gene therapy.
- This research may reduce the toxicity associated with adenovirus-based therapies.
