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Viruses and the TNF-related cytokines, an evolving battle
1Division of Molecular Immunology, La Jolla Institute for Allergy and Immunology, 10355 Science Center Drive, San Diego, CA 92121, USA. benedict@liai.org
Abstract:
Tumor necrosis factor (TNF)-related cytokines are critical effector molecules in the immune response to viral pathogens. Engagement of the TNF receptors by their cognate ligands activates apoptotic and non-apoptotic signaling pathways, both of which can mediate antiviral activity. In response, viruses have evolved mechanisms to inhibit signaling by some cytokines of the TNF superfamily. These strategies are largely unique to each class of virus, but are similar in that they all target key regulatory checkpoints of the TNF pathway. In recent years, studies directed towards dissecting the mechanisms of TNF signaling and the viral retort have led to several significant discoveries, and form the basis for this review.
Insights
Tumor necrosis factor (TNF)-related cytokines fight viral infections by activating immune signaling. Viruses counteract this by evolving unique strategies to inhibit TNF pathway checkpoints, a key area of recent research.
Area of Science:
- Immunology
- Virology
- Molecular Biology
Background:
- Tumor necrosis factor (TNF)-related cytokines are crucial for antiviral immune responses.
- TNF receptor (TNFR) engagement triggers both apoptotic and non-apoptotic signaling pathways with antiviral effects.
- Viruses have developed diverse mechanisms to evade or inhibit TNFR signaling.
Purpose of the Study:
- To review the intricate mechanisms of TNF signaling in antiviral immunity.
- To explore the viral strategies employed to subvert TNF superfamily signaling.
- To highlight recent discoveries in the interplay between viral evasion and host TNF pathways.
Main Methods:
- Literature review of studies on TNF signaling and viral inhibition.
- Analysis of molecular mechanisms underlying TNFR activation and viral interference.
- Synthesis of current knowledge on viral countermeasures against TNF pathways.
Main Results:
- TNF signaling pathways are essential for controlling viral infections.
- Viral evasion strategies target critical regulatory points in the TNF pathway.
- These viral strategies are virus-specific but converge on TNF pathway disruption.
Conclusions:
- Understanding viral inhibition of TNF signaling is key to antiviral immunity.
- Viral countermeasures highlight the importance of TNF pathways in host defense.
- Continued research into these interactions offers insights into novel therapeutic targets.