Mitogen-Activated Protein Kinases: Therapeutic Signaling Catalysts in Viral Immune Evasion

Area of Science:

• Immunology
• Virology
• Molecular Biology

Background:

• Mitogen-activated protein kinase (MAPK) pathways (ERK, JNK, p38) are crucial for regulating immune responses during viral infections.
• Viruses frequently manipulate MAPK signaling to facilitate immune evasion, replication, and chronic infection.
• The CD1d-invariant natural killer T (iNKT) cell axis is vital for early antiviral immunity but is often dysregulated by MAPK-dependent viral strategies.

Purpose of the Study:

• To review how diverse viruses, including HSV-1, HBV, HCMV, and SARS-CoV-2, manipulate MAPK signaling pathways.
• To elucidate the impact of MAPK pathway alterations on antigen-presenting cells, T cell exhaustion, and immune cell metabolism in viral infections.
• To examine the therapeutic potential and challenges of targeting MAPK pathways for antiviral immunity.

Main Methods:

• Literature review of viral manipulation of MAPK signaling pathways.
• Analysis of MAPK-dependent mechanisms affecting the CD1d-iNKT cell axis and immune cell functions.
• Evaluation of current and potential therapeutic strategies targeting MAPK pathways in viral infections.

Main Results:

• Viruses like HSV-1, HBV, HCMV, and SARS-CoV-2 hijack MAPK pathways to disrupt host immune functions.
• MAPK pathway dysregulation contributes to impaired antigen presentation, T cell exhaustion, and altered immune cell metabolism, aiding viral evasion.
• Targeting MAPK pathways can modulate immune responses, but requires precise timing and context-specific application to balance efficacy and safety.

Conclusions:

• MAPK pathways are central targets for viral immune evasion strategies.
• Targeting MAPK signaling presents a promising avenue for antiviral therapies, but requires careful optimization to avoid detrimental effects on protective immunity.
• Further research into selective, host-directed antiviral strategies targeting MAPK pathways is warranted.