Coronaviruses are a major health care threat to humankind. Currently, the host factors that contribute to limit disease severity in healthy young patients are not well defined.
Interferons are key
antiviral molecules, especially type I and
type III interferons. The role of these
interferons during coronavirus disease is a subject of debate. Here, using mice that are deficient in type I (IFNAR1-/-), type III (IFNLR1-/-), or both (IFNAR1/LR1-/-)
interferon signaling pathways and murine-adapted coronavirus (MHV-A59) administered through the intranasal route, we define the role of
interferons in
coronavirus infection. We show that
type I interferons play a major role in host survival in this model, while a minimal role of
type III interferons was manifested only in the absence of
type I interferons or during a lethal dose of coronavirus. IFNAR1-/- and IFNAR1/LR1-/- mice had an uncontrolled viral burden in the airways and lung and increased viral dissemination to other organs. The absence of only
type III interferon signaling had no measurable difference in the viral load. The increased viral load in IFNAR1-/- and IFNAR1/LR1-/- mice was associated with increased tissue injury, especially evident in the lung and liver. Type I but not
type III interferon treatment was able to promote survival if treated during early disease. Further, we show that
type I interferon signaling in macrophages contributes to the beneficial effects during
coronavirus infection in mice. IMPORTANCE The
antiviral and pathological potential of type I and
type III interferons during
coronavirus infection remains poorly defined, and opposite findings have been reported. We report that both type I and
type III interferons have anticoronaviral activities, but their potency and organ specificity differ.
Type I interferon deficiency rendered the mice susceptible to even a sublethal murine coronavirus
infection, while the
type III interferon deficiency impaired survival only during a lethal
infection or during a sublethal
infection in the absence of
type I interferon signaling. While treatment with both type I and III
interferons promoted viral clearance in the airways and lung, only
type I interferons promoted the viral clearance in the liver and improved host survival upon early treatment (12 h postinfection). This study demonstrates distinct roles and potency of type I and
type III interferons and their therapeutic potential during coronavirus lung
infection.