title: Inducible interleukin 32 (IL-32) exerts extensive antiviral function via selective stimulation of interferon λ1 (IFN-λ1).
abstract: Interleukin (IL)-32 has been recognized as a proinflammatory cytokine that participates in responses to viral infection. However, little is known about how IL-32 is induced in response to viral infection and the mechanisms of IL-32-mediated antiviral activities. We discovered that IL-32 is elevated by hepatitis B virus (HBV) infection both in vitro and in vivo and that HBV induced IL-32 expression at the level of both transcription and post-transcription. Furthermore, microRNA-29b was found to be a key factor in HBV-regulated IL-32 expression by directly targeting the mRNA 3'-untranslated region of IL-32. Antiviral analysis showed that IL-32 was not sufficient to alter HBV replication in HepG2.2.15 cells. To mimic the viremic phase of viral infection, freshly isolated peripheral blood mononuclear cells were treated with IL-32γ, the secretory isoform, and the supernatants were used for antiviral assays. Surprisingly, these supernatants exhibited extensive antiviral activity against multiplex viruses besides HBV. Thus, we speculated that the IL-32γ-treated peripheral blood mononuclear cells produced and secreted an unknown antiviral factor. Using antibody neutralization assays, we identified the factor as interferon (IFN)-λ1 and not IFN-α. Further studies indicated that IL-32γ effectively inhibited HBV replication in a hydrodynamic injection mouse model. Clinical data showed that elevated levels of IFN-λ1 both in serum and liver tissue of HBV patients were positively correlated to the increased levels of IL-32. Our results demonstrate that elevated IL-32 levels during viral infection mediate antiviral effects by stimulating the expression of IFN-λ1.
authors.affiliation: From The State Key Laboratory of Virology, College of Life Sciences, and Chinese-French Liver Disease Research Institute at Zhongnan Hospital, Wuhan University, Wuhan 430072, China and; the Research Center for Tissue Engineering and Regenerative Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
authors.forename: Yongkui
authors.initials: Y
authors.lastname: Li
authors.affiliation: From The State Key Laboratory of Virology, College of Life Sciences, and Chinese-French Liver Disease Research Institute at Zhongnan Hospital, Wuhan University, Wuhan 430072, China and.
authors.forename: Jiajia
authors.initials: J
authors.lastname: Xie
authors.affiliation: From The State Key Laboratory of Virology, College of Life Sciences, and Chinese-French Liver Disease Research Institute at Zhongnan Hospital, Wuhan University, Wuhan 430072, China and.
authors.forename: Xiupeng
authors.initials: X
authors.lastname: Xu
authors.affiliation: From The State Key Laboratory of Virology, College of Life Sciences, and Chinese-French Liver Disease Research Institute at Zhongnan Hospital, Wuhan University, Wuhan 430072, China and.
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.affiliation: From The State Key Laboratory of Virology, College of Life Sciences, and Chinese-French Liver Disease Research Institute at Zhongnan Hospital, Wuhan University, Wuhan 430072, China and.
authors.forename: Yushun
authors.initials: Y
authors.lastname: Wan
authors.affiliation: From The State Key Laboratory of Virology, College of Life Sciences, and Chinese-French Liver Disease Research Institute at Zhongnan Hospital, Wuhan University, Wuhan 430072, China and.
authors.forename: Yingle
authors.initials: Y
authors.lastname: Liu
authors.affiliation: From The State Key Laboratory of Virology, College of Life Sciences, and Chinese-French Liver Disease Research Institute at Zhongnan Hospital, Wuhan University, Wuhan 430072, China and.
authors.forename: Chengliang
authors.initials: C
authors.lastname: Zhu
authors.affiliation: From The State Key Laboratory of Virology, College of Life Sciences, and Chinese-French Liver Disease Research Institute at Zhongnan Hospital, Wuhan University, Wuhan 430072, China and. Electronic address: yingzhu@whu.edu.cn.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhu
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000378:metabolism*; D001665:Binding Sites; D002460:Cell Line; D005786:Gene Expression Regulation / Q000187:drug effects; D006515:Hepatitis B virus / Q000187:drug effects / Q000502:physiology*; D019694:Hepatitis B, Chronic / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000821:virology; D006801:Humans; D057446:Hydrodynamics; D007372:Interferons; D007378:Interleukins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism / Q000821:virology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects; D000095022:Interferon Lambda
chemical_list: D000998:Antiviral Agents; D007372:Interferons; D007378:Interleukins; D035683:MicroRNAs; D016328:NF-kappa B; D011994:Recombinant Proteins; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C496971:IL32 protein, human; C532045:MIRN29a microRNA, human
keywords: Cytokines/Interferon; Gene Regulation; Host-Pathogen Interactions; Infectious Diseases; Interleukin; Viral Immunology