Reactive oxygen species oxidize STING and suppress interferon production

Area of Science:

• Immunology
• Virology
• Cellular Biology

Background:

• Reactive oxygen species (ROS) are cellular respiration by-products linked to oxidative stress.
• ROS play a role in host defense against pathogens.
• Some viruses, like herpesviruses, appear to benefit from ROS-induced conditions, but mechanisms are unclear.

Purpose of the Study:

• To investigate the role of ROS in antiviral immunity during herpesvirus infection.
• To elucidate the molecular mechanisms by which ROS affect the interferon response.

Main Methods:

• Murine herpesvirus infection model.
• Analysis of interferon response pathways.
• Biochemical assays to detect protein oxidation and STING polymerization.

Main Results:

• ROS were found to impair the interferon response downstream of cytoplasmic DNA sensing during murine herpesvirus infection.
• ROS suppressed the type I interferon response by oxidizing Cysteine 147 on murine STING (stimulator of interferon genes).
• Oxidation of Cysteine 147 inhibited STING polymerization and downstream signaling, thereby reducing interferon production.

Conclusions:

• Redox regulation of STING, specifically Cysteine 147 in mice (equivalent to Cysteine 148 in humans), controls interferon production.
• ROS actively orchestrate antiviral immune responses.
• Viruses can exploit the ROS-mediated suppression of interferon to evade host defenses.