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Virology. 2015 Aug;482:181-8. doi: 10.1016/j.virol.2015.03.048. Epub 2015 Apr 11.

RIG-I and TLR3 are both required for maximum interferon induction by influenza virus in human lung alveolar epithelial cells.

Author information

1
Pulmonary and Critical Care Division, Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
2
Section of Molecular Medicine, Department of Internal Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA; Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
3
Pulmonary and Critical Care Division, Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA; Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA; Veterans Affairs Medical Center, Oklahoma City, OK, USA. Electronic address: jordan-metcalf@ouhsc.edu.

Abstract

Pattern recognition receptors, such as retinoic acid-inducible protein I (RIG-I), Toll-like receptors 3 and 7 (TLR3 and 7), and nucleotide-binding oligomerization domain containing protein 2 (NOD2), play important roles in the recognition of influenza A virus (IAV), but their role in interferon (IFN) induction is still unclear, particularly in human lung. We investigated IFN induction by IAV in the A549 cell line as well as in primary human alveolar epithelial cells (AEC). TLR3/7, NOD2, RIG-I, and IFN expression levels were measured by qRT-PCR and ELISA in cells infected with IAV PR8. We found that TLR7 and NOD2 were not involved in IFN induction by IAV in these cells. Neither RIG-I nor TLR3 siRNA alone completely blocked IFN induction. However, double knockdown of RIG-I and TLR3 completely inhibited IFN induction by influenza. Thus, signaling through both RIG-I and TLR3 is important for IFN induction by IAV in human lung AEC.

KEYWORDS:

A549; AEC; Human; Influenza; Innate immunity; Interferon; Lung; PR8; RIG-I; TLR3

PMID:
25880109
PMCID:
PMC4461467
DOI:
10.1016/j.virol.2015.03.048
[Indexed for MEDLINE]
Free PMC Article

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