Mitochondrial reactive oxygen species modulate innate immune response to influenza A virus in human nasal epithelium

Sujin Kim, Min Ji Kim, Do Yang Park, Hyo Jin Chung, Chang Hoon Kim, Joo Heon Yoon, Hyun Jik Kim

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)

Abstract

The innate immune system of the nasal epithelium serves as a first line of defense against invading respiratory viruses including influenza A virus (IAV). Recently, it was verified that interferon (IFN)-related immune responses play a critical role in local antiviral innate immunity. Reactive oxygen species (ROS) generation by exogenous pathogens has also been demonstrated in respiratory epithelial cells and modulation of ROS has been reported to be important for respiratory virus-induced innate immune mechanisms. Passage-2 normal human nasal epithelial (NHNE) cells were inoculated with IAV (WS/33, H1N1) to assess the sources of IAV-induced ROS and the relationship between ROS and IFN-related innate immune responses. Both STAT1 and STAT2 phosphorylation and the mRNA levels of IFN-stimulated genes, including Mx1, 2,5-OAS1, IFIT1, and CXCL10, were induced after IAV infection up to three days post infection. Similarly, we observed that mitochondrial ROS generation increased maximally at 2 days after IAV infection. After suppression of mitochondrial ROS generation, IAV-induced phosphorylation of STAT and mRNA levels of IFN-stimulated genes were attenuated and actually, viral titers of IAV were significantly higher in cases with scavenging ROS. Our findings suggest that mitochondrial ROS might be responsible for controlling IAV infection and may be potential sources of ROS generation, which is required to initiate an innate immune response in NHNE cells.

Original languageEnglish
Pages (from-to)78-83
Number of pages6
JournalAntiviral Research
Volume119
DOIs
Publication statusPublished - 2015 Jul 1

Bibliographical note

Funding Information:
This work was supported by the National Research Foundation of the Korean Government (Ministry of Science, ICT & Future Planning, MSIP ), grant 2007-0056092 (J.H.Y.), National Research Foundation of Korea ( NRF ) funded by the Ministry of Science, ICT & Future Planning ( 2012M3A9C5048709 ) (J.H.Y.), National Research Foundation of Korea (NRF) grant funded by the Korean Government (MSIP) ( 2014R1A2A01003385 ) (J.H.Y.) and the Basic Science Research Program of the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology grant 2013R1A1A2011612 (H.J.K.).

Publisher Copyright:
© 2015 Elsevier B.V.

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Virology

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