title: The Superiority of IFN-λ as a Therapeutic Candidate to Control Acute Influenza Viral Lung Infection.
abstract: 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.
authors.affiliation: 1 BK 21 Project for Medical Science.
authors.forename: Sujin
authors.initials: S
authors.lastname: Kim
authors.affiliation: 2 Research Center for Human Natural Defense System.
authors.forename: Min-Ji
authors.initials: MJ
authors.lastname: Kim
authors.affiliation: 2 Research Center for Human Natural Defense System.|3 The Airway Mucus Institute, and.|4 Department of Otorhinolaryngology, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Chang-Hoon
authors.initials: CH
authors.lastname: Kim
authors.affiliation: 5 Department of Otorhinolaryngology, Jeju National University, Jeju, Korea.
authors.forename: Ju Wan
authors.initials: JW
authors.lastname: Kang
authors.affiliation: 6 American School of Paris, Paris, France; and.
authors.forename: Ha Kyung
authors.initials: HK
authors.lastname: Shin
authors.affiliation: 7 Department of Otorhinolaryngology, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Dong-Young
authors.initials: DY
authors.lastname: Kim
authors.affiliation: 7 Department of Otorhinolaryngology, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Tae-Bin
authors.initials: TB
authors.lastname: Won
authors.affiliation: 7 Department of Otorhinolaryngology, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Doo Hee
authors.initials: DH
authors.lastname: Han
authors.affiliation: 7 Department of Otorhinolaryngology, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Chae Seo
authors.initials: CS
authors.lastname: Rhee
authors.affiliation: 1 BK 21 Project for Medical Science.|2 Research Center for Human Natural Defense System.|3 The Airway Mucus Institute, and.|4 Department of Otorhinolaryngology, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Joo-Heon
authors.initials: JH
authors.lastname: Yoon
authors.affiliation: 3 The Airway Mucus Institute, and.|7 Department of Otorhinolaryngology, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Hyun Jik
authors.initials: HJ
authors.lastname: Kim
mesh_terms: D000208:Acute Disease; D000281:Administration, Intranasal; D000818:Animals; D057134:Antibodies, Neutralizing / Q000494:pharmacology; D007113:Immunity, Innate / Q000187:drug effects; D016899:Interferon-beta / Q000494:pharmacology / Q000627:therapeutic use; D007378:Interleukins / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D007700:Kinetics; D008168:Lung / Q000187:drug effects / Q000473:pathology / Q000821:virology*; D008297:Male; D008810:Mice, Inbred C57BL; D009976:Orthomyxoviridae Infections / Q000188:drug therapy* / Q000821:virology*
chemical_list: D057134:Antibodies, Neutralizing; D007378:Interleukins; D016899:Interferon-beta
keywords: IFN-β; IFN-λ2/3; acute viral lung infection; influenza A virus