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The Induction of Pattern-Recognition Receptor Expression against Influenza A Virus through Duox2-Derived Reactive Oxygen Species in Nasal Mucosa

 Hyun Jik Kim  ;  Chang-Hoon Kim  ;  Min-Ji Kim  ;  Ji-Hwan Ryu  ;  Sang Yeop Seong  ;  Sujin Kim  ;  Su Jin Lim  ;  Michael J. Holtzman  ;  Joo-Heon Yoon 
 American Journal of Respiratory Cell and Molecular Biology, Vol.53(4) : 525-535, 2015 
Journal Title
 American Journal of Respiratory Cell and Molecular Biology 
Issue Date
Animals ; Cell Line ; DEAD-box RNA Helicases/genetics ; DEAD-box RNA Helicases/metabolism* ; Dual Oxidases ; Humans ; Influenza A virus/immunology* ; Influenza, Human/immunology ; Influenza, Human/metabolism* ; Influenza, Human/virology ; Interferon-Induced Helicase, IFIH1 ; Male ; Membrane Proteins/genetics ; Membrane Proteins/metabolism* ; Mice, Inbred C57BL ; NADPH Oxidases/genetics ; NADPH Oxidases/metabolism ; Nasal Mucosa/metabolism* ; Nasal Mucosa/virology ; Nerve Tissue Proteins/genetics ; Nerve Tissue Proteins/metabolism* ; Reactive Oxygen Species/metabolism ; Toll-Like Receptor 3/genetics ; Toll-Like Receptor 3/metabolism ; Transcriptional Activation/immunology*
Duox2 ; influenza A virus ; melanoma differentiation–associated protein 5 ; reactive oxygen species ; retinoic acid–inducible gene-I
We studied the relative roles of Duox2-derived reactive oxygen species (ROS) in host defense against influenza A virus (IAV) infection in normal human nasal epithelial cells and mouse nasal mucosa. We found that Duox2 primarily generated ROS rapidly after IAV infection in normal human nasal epithelial cells and that knockdown of Duox2 aggravated IAV infection. In addition, Duox2-derived ROS enhancement significantly suppressed IAV infection in nasal epithelium. In particular, Duox2-derived ROS were required for the induction of retinoic acid-inducible gene (RIG)-I and melanoma differentiation-associated protein 5 (MDA5) transcription. After intranasal IAV inoculation into mice, viral infection was significantly aggravated from 3 days postinoculation (dpi) in the nasal mucosa, and the IAV viral titer was highest at 7 dpi. Both RIG-I and MDA5 messenger RNA levels increased dominantly in mouse nasal mucosa from 3 dpi; consistent with this, RIG-I and MDA5 proteins were also induced after IAV infection. RIG-I and MDA5 messenger RNA levels were induced to a lower extent in the nasal mucosa of the mice that were inoculated with Duox2 short hairpin RNA, and the IAV viral titer was significantly higher in nasal lavage. Taken together, Duox2-derived ROS are necessary for the innate immune response and trigger the induction of RIG-I and MDA5 to resist IAV infection in human nasal epithelium and mouse nasal mucosa.
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1. College of Medicine (의과대학) > Dept. of Otorhinolaryngology (이비인후과학교실) > 1. Journal Papers
5. Research Institutes (연구소) > Research Center for Human Natural Defense System (생체방어연구센터) > 1. Journal Papers
Yonsei Authors
Kim, Chang Hoon(김창훈) ORCID logo https://orcid.org/0000-0003-1238-6396
Seong, Sang Yeob(성상엽)
Ryu, Ji Hwan(유지환)
Yoon, Joo Heon(윤주헌)
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