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Antiviral Res. 2015 Jul;119:78-83. doi: 10.1016/j.antiviral.2015.04.011. Epub 2015 Apr 28.

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

Author information

1
Research Center for Natural Human Defense System, Yonsei University College of Medicine, Seoul, Republic of Korea.
2
Department of Otorhinolaryngology, Yonsei University College of Medicine, Seoul, Republic of Korea.
3
Department of Otorhinolaryngology, Yonsei University College of Medicine, Seoul, Republic of Korea; The Airway Mucus Institute, Yonsei University College of Medicine, Seoul, Republic of Korea.
4
Department of Otorhinolaryngology, Yonsei University College of Medicine, Seoul, Republic of Korea; The Airway Mucus Institute, Yonsei University College of Medicine, Seoul, Republic of Korea; BK 21 Project for Medical Science, Yonsei University College of Medicine, Seoul, Republic of Korea; Research Center for Natural Human Defense System, Yonsei University College of Medicine, Seoul, Republic of Korea.
5
The Airway Mucus Institute, Yonsei University College of Medicine, Seoul, Republic of Korea; Department of Otorhinolaryngology, Seoul National University College of Medicine, Seoul, Republic of Korea. Electronic address: hyunjerry@snu.ac.kr.

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.

KEYWORDS:

Influenza A virus; Interferon-stimulated genes; Mitochondria; Reactive oxygen species

PMID:
25930096
DOI:
10.1016/j.antiviral.2015.04.011
[Indexed for MEDLINE]

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