STING Restricts EV-A71 Infection by Regulating T Cell Development and Enhancing Immune Cell Effector Function

Area of Science:

• Immunology
• Virology
• Molecular Biology

Background:

• Enterovirus A71 (EV-A71) infection can activate STING signaling pathways in vitro.
• The in vivo role of STING and its immune regulatory mechanisms in EV-A71 infection are not fully understood.

Purpose of the Study:

• To investigate the role and mechanism of STING in regulating EV-A71 infection in vivo.
• To explore STING's impact on immune responses during EV-A71 infection.

Main Methods:

• Utilized STING-specific agonist diABZI to activate STING.
• Employed STING-knockout mice to assess STING's function in EV-A71 infection.
• Analyzed viral replication, clinical symptoms, survival rates, immune cell populations, and cytokine profiles.

Main Results:

• STING activation inhibited EV-A71 replication, reduced symptoms, and increased survival in mice.
• STING knockout exacerbated viral replication, lethality, and disease severity.
• STING activation promoted interferon signaling, upregulated interferon-stimulated genes (ISGs), modulated cytokine profiles, and expanded immune cell populations (T cells, NK cells, myeloid cells).
• STING knockout impaired T cell development and reduced CD8+ T cell and NK cell effector functions.

Conclusions:

• STING activation effectively suppresses EV-A71 replication and alleviates infection symptoms by modulating immune and inflammatory responses.
• Findings provide a framework for understanding STING's role in antiviral immunity.
• Suggests potential for STING-targeted therapies against viral infections.