Gene Expression and Antiviral Activity of Interleukin-35 in Response to Influenza A Virus Infection.
Interleukin-35 (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-κB. IL-35 expression was significantly suppressed by selective inhibitors of cyclooxygenase-2 (COX-2) and inducible nitric-oxide synthase, 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, including double-stranded RNA-dependent protein kinase, 2',5'-oligoadenylate synthetase, and myxovirus resistance protein. 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.
From the The State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, Hubei 430072, China.
Li
L
Wang
From the The State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, Hubei 430072, China.
Shengli
S
Zhu
From the The State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, Hubei 430072, China.
Gang
G
Xu
From the The State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, Hubei 430072, China.
Jian
J
Feng
From the The State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, Hubei 430072, China.
Tao
T
Han
From the The State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, Hubei 430072, China.
Fanpeng
F
Zhao
From the The State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, Hubei 430072, China.
Ying-Long
YL
She
From the The State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, Hubei 430072, China.
Shi
S
Liu
From the The State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, Hubei 430072, China.
Linbai
L
Ye
From the The State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, Hubei 430072, China yingzhu@whu.edu.cn.
Ying
Y
Zhu
D000072283:A549 Cells; D051546:Cyclooxygenase 2 / Q000276:immunology; D005786:Gene Expression Regulation / Q000276:immunology*; D006509:Hepatitis B / Q000276:immunology; D006515:Hepatitis B virus / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate; D009980:Influenza A virus / Q000276:immunology*; D007251:Influenza, Human / Q000276:immunology*; D007370:Interferon Type I / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology; D007378:Interleukins / Q000276:immunology*; D019169:Jurkat Cells; D016328:NF-kappa B / Q000276:immunology
D007370:Interferon Type I; D007378:Interleukins; D016328:NF-kappa B; C532417:interleukin-35, human; D007371:Interferon-gamma; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human
NF-κB (NF-KB); antiviral agent; host defense; host-pathogen interaction; influenza virus; innate immunity; interferon; interleukin; viral infection