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The Superiority of IFN-λ as a Therapeutic Candidate to Control Acute Influenza Viral Lung Infection

 Sujin Kim  ;  Min-Ji Kim  ;  Chang-Hoon Kim  ;  Ju Wan Kang  ;  Ha Kyung Shin  ;  Dong-Young Kim  ;  Tae-Bin Won  ;  Doo Hee Han  ;  Chae Seo Rhee  ;  Joo-Heon Yoon  ;  Hyun Jik Kim 
 American Journal of Respiratory Cell and Molecular Biology, Vol.56(2) : 202-212, 2017 
Journal Title
 American Journal of Respiratory Cell and Molecular Biology 
Issue Date
Acute Disease ; Administration, Intranasal ; Animals ; Antibodies, Neutralizing/pharmacology ; Immunity, Innate/drug effects ; Interferon-beta/pharmacology ; Interferon-beta/therapeutic use ; Interleukins/administration & dosage ; Interleukins/pharmacology ; Interleukins/therapeutic use* ; Kinetics ; Lung/drug effects ; Lung/pathology ; Lung/virology* ; Male ; Mice, Inbred C57BL ; Orthomyxoviridae Infections/drug therapy* ; Orthomyxoviridae Infections/virology*
IFN-β ; IFN-λ2/3 ; acute viral lung infection ; influenza A virus
Here, we studied the IFN-regulated innate immune response against influenza A virus (IAV) infection in the mouse lung and the therapeutic effect of IFN-λ2/3 in acute IAV lung infection. For viral infections, IAV (WS/33, H1N1, PR8 H1N1, H5N1) were inoculated into wild-type mice by intranasal delivery, and IAV mRNA level and viral titer were measured. To compare the antiviral effect of IFNs in vivo in the lung, neutralizing antibodies and recombinant IFNs were used. After intranasal inoculation of IAV into mice, viral infection peaked at 7 days postinfection, and the IAV titer also reached its peak at this time. We found that IFN-β and IFN-λ2/3 were preferentially induced after IAV infection and the IFN-λ2/3-mediated innate immune response was specifically required for the induction of IFN-stimulated genes (ISGs) transcription in the mouse respiratory tract. Neutralization of secreted IFN-λ2/3 aggravated acute IAV lung infection in mice with intact IFN-β induction; consistent with this finding, the transcription of ISGs was significantly reduced. Intranasal administration of IFN-λ2/3 significantly suppressed various strains of IAV infection, including WS/33 (H1N1), PR (H1N1), and H5N1 in the mouse lung, and was accompanied by greater up-regulation of ISGs. Taken together, our data indicate that the IFN-λ2/3-mediated innate immune response is necessary to protect the lungs from IAV infection, and intranasally delivered IFN-λ2/3 has the potential to be a useful therapeutic strategy for treating acute IAV lung infection.
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1. College of Medicine (의과대학) > Dept. of Otorhinolaryngology (이비인후과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Chang Hoon(김창훈) ORCID logo https://orcid.org/0000-0003-1238-6396
Yoon, Joo Heon(윤주헌)
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