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 KotenkoSusan Compton, Craig B. Wilen, Andrew Wang, Charles S. Dela Cruz

Research output: Contribution to journalArticlepeer-review


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 (IFNAR12/2), type III (IFNLR12/2), or both (IFNAR1/LR12/2) 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. IFNAR12/2 and IFNAR1/LR12/2 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 IFNAR12/2 and IFNAR1/LR12/2 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.

Original languageAmerican English
Article numbere01241-21
JournalJournal of virology
Issue number2
StatePublished - Jan 2022
Externally publishedYes

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology


  • Antiviral agents
  • Coronavirus
  • Lung defense
  • Type I interferons
  • Type III interferons


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