Distinct Roles of Type I and Type III Interferons during a Native Murine β Coronavirus Lung Infection

Area of Science:

• Immunology
• Virology

Background:

• Coronaviruses pose a significant global health threat.
• Host factors influencing coronavirus disease severity are not fully understood.
• The roles of type I and type III interferons in coronavirus infections are debated.

Purpose of the Study:

• To define the distinct roles of type I and type III interferons in coronavirus infection.
• To investigate the therapeutic potential of interferons in a murine coronavirus model.

Main Methods:

• Utilized mice deficient in type I (IFNAR1-/-), type III (IFNLR1-/-), or both interferon signaling pathways.
• Infected mice intranasally with a murine-adapted coronavirus (MHV-A59).
• Assessed viral burden, tissue injury, and host survival.

Main Results:

• Type I interferons are essential for host survival and controlling viral burden in airways, lungs, and other organs.
• Type III interferons showed a minimal role, primarily in lethal infections or when type I signaling was absent.
• Type I interferon treatment improved survival and viral clearance, particularly in the liver, when administered early.

Conclusions:

• Type I interferons play a dominant role in host defense against coronaviruses, while type III interferons have a more limited, context-dependent function.
• Distinct organ-specific activities and potencies of type I and type III interferons were demonstrated.
• Type I interferons hold significant therapeutic potential for coronavirus lung infections.