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J Biol Chem. 2013 Jul 19;288(29):20927-41. doi: 10.1074/jbc.M112.440115. Epub 2013 May 31.

Inducible interleukin 32 (IL-32) exerts extensive antiviral function via selective stimulation of interferon λ1 (IFN-λ1).

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1
State Key Laboratory of Virology, College of Life Sciences, and Chinese-French Liver Disease Research Institute at Zhongnan Hospital, Wuhan University, Wuhan 430072, China.

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.

KEYWORDS:

Cytokines/Interferon; Gene Regulation; Host-Pathogen Interactions; Infectious Diseases; Interleukin; Viral Immunology

PMID:
23729669
PMCID:
PMC3774363
DOI:
10.1074/jbc.M112.440115
[Indexed for MEDLINE]
Free PMC Article
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