Dengue Virus Infection: Immune Response and Therapeutic Targets.

Area of Science:

• Immunology and Virology
• Molecular Biology

Background:

• Dengue virus (DENV) infection is a significant global health concern with high incidence and mortality.
• The DENV immune response is paradoxical, contributing to both viral clearance and severe disease, exacerbated by cross-reactivity between serotypes.
• Developing a universal flavivirus vaccine is challenging due to DENV serotype complexity.

Purpose of the Study:

• To review the roles of high motility group box 1 (HMGB1) and NLRP3 inflammasome activation in DENV pathogenesis.
• To highlight HMGB1 and NLRP3 inflammasome inhibitors as potential therapeutic targets for DENV infection.

Main Methods:

• Literature review focusing on the molecular mechanisms of DENV-induced inflammation and cell death.
• Analysis of the downstream signaling pathways involving nuclear factor κB (NF-κB) and pro-inflammatory cytokines IL-1β and IL-18.
• Examination of NLRP3's role in cellular apoptosis and pyroptosis.

Main Results:

• HMGB1 and NLRP3 inflammasome activation are key drivers of inflammatory responses in DENV infection.
• These pathways lead to the release of IL-1β and IL-18 via NF-κB activation.
• NLRP3 inflammasome activation contributes to cellular apoptosis and pyroptosis, potentially causing systemic failure.

Conclusions:

• Understanding the immunopathogenesis of DENV infection has advanced significantly.
• HMGB1 and NLRP3 inflammasome inhibitors represent promising therapeutic avenues to mitigate DENV disease severity.
• While effective antivirals or vaccines are lacking, immunomodulatory approaches offer hope for managing DENV infections.