Gene expression and antiviral activity of interleukin-35 in response to influenza A virus infection.

Gene expression and antiviral activity of interleukin-35 in response to influenza A virus infection.

J Biol Chem. 2016 Jun 15;

Authors: Wang L, Zhu S, Xu G, Feng J, Han T, Zhao F, She YL, Liu S, Ye L, Zhu Y

Abstract
Interleukin (IL)-35 is a newly described member of the IL-12 family. It has been reported to inhibit inflammation and autoimmune inflammatory disease, and can increase apoptotic sensitivity. Little is known about the role of IL-35 during viral infection. Herein, high levels of IL-35 were found in peripheral blood mononuclear cells and throat swabs from patients with seasonal influenza A virus (IAV) relative to healthy individuals. IAV infection of human lung epithelial and primary cells increased levels of IL-35 mRNA and protein. Further studies demonstrated that IAV-induced IL-35 transcription is regulated by NF-kB. IL-35 expression was significantly suppressed by selective inhibitors of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS), indicating their involvement in IL-35 expression. Interestingly, IL-35 production may have suppressed IAV RNA replication and viral protein synthesis via induction of type I and III interferons (IFN), leading to activation of downstream IFN effectors, PKR,OAS, and Mx. IL-35 exhibited extensive antiviral activity against the hepatitis B virus, enterovirus 71, and vesicular stomatitis virus. Our results demonstrate that IL-35 is a novel IAV-inducible cytokine, and its production elicits antiviral activity.

PMID: 27307042 [PubMed - as supplied by publisher]

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