Distinct Roles of Type I and Type III Interferons during a Native Murine β Coronavirus Lung Infection
Lokesh Sharma, Xiaohua Peng, Hua Qing, Brandon K. Hilliard, Jooyoung Kim, Anush Swaminathan, Justin Tian, Kavita Israni-Winger, Cuiling Zhang, Victoria Habet, Lin Wang, Gayatri Gupta, Xuefei Tian, Yina Ma, Hyeon-Jun Shin, Sang-Hun Kim, Min-Jong Kang, Shuta Ishibe, Lawrence H. Young, Sergei Kotenko, Susan Compton, Craig B. Wilen, Andrew Wang, Charles S. Dela Cruz
Abstract
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.