title: Protection from RNA and DNA viruses by IL-32.
abstract: Several studies have documented a proinflammatory role for IL-32, which induces IL-1α, IL-1β, IL-6, TNF, and chemokines via NF-κB, p38MAPK, and AP-1. However, IL-32 also participates in the responses to infection with viruses such as HIV-1 and influenza. In this study, we explored these antiviral properties of IL-32. Vital staining assays demonstrated that low concentrations (5-10 ng/ml) of rIL-32γ protected epithelial WISH cells from vesicular stomatitis virus-induced cell death. By lactate dehydrogenase assays, treatment with IL-32γ resulted in a 3- to 4-fold decrease in viral load. Specific silencing of IL-32 revealed that the antiviral responses triggered by the synthetic analogs of ssRNA viruses (polyuridine) and dsRNA viruses (polyinosinic-polycytidylic acid) were significantly weaker (2- to 3-fold more virus) in WISH cells in the absence of IL-32. Importantly, we discovered that the polyinosinic-polycytidylic acid-induced increase in production of IFN-α in human PBMC was nearly completely abolished when IL-32 was silenced. Moreover, we observed that IL-32 antagonizes the DNA virus HSV-2 in epithelial Vero cells as well as in human umbilical cord endothelial cells, as production of HSV-2 increased 8-fold upon silencing of IL-32 (p < 0.001). Mechanistically, we found that IL-32 used the PKR-eIF-2α as well as the MxA antiviral pathways. Unexpectedly, a considerable part of the antiviral properties of IL-32 was not dependent on IFNs; specific blockade of IFN activity reduced the antiviral properties of IL-32 only moderately. In conclusion, these data suggest a central role for IL-32 in the immune response to RNA and DNA viruses, which may be exploitable for clinical use in the future.
authors.affiliation: Department of Medicine, University of Colorado Denver, Aurora, CO 80045, USA.
authors.forename: Jarod A
authors.initials: JA
authors.lastname: Zepp
authors.forename: Claudia A
authors.initials: CA
authors.lastname: Nold-Petry
authors.forename: Charles A
authors.initials: CA
authors.lastname: Dinarello
authors.forename: Marcel F
authors.initials: MF
authors.lastname: Nold
mesh_terms: D000818:Animals; D002460:Cell Line; D002522:Chlorocebus aethiops; D003588:Cytopathogenic Effect, Viral / Q000276:immunology; D004730:Endothelium, Vascular / Q000276:immunology / Q000473:pathology / Q000821:virology; D006558:Herpes Genitalis / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D018258:Herpesvirus 2, Human / Q000276:immunology* / Q000472:pathogenicity*; D006801:Humans; D018836:Inflammation Mediators / Q000502:physiology* / Q000627:therapeutic use; D007378:Interleukins / Q000502:physiology* / Q000627:therapeutic use; D007770:L-Lactate Dehydrogenase; D014709:Vero Cells; D054243:Vesicular Stomatitis / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D014721:Vesicular stomatitis Indiana virus / Q000276:immunology* / Q000472:pathogenicity*; D019562:Viral Load / Q000276:immunology
chemical_list: C496971:IL32 protein, human; D018836:Inflammation Mediators; D007378:Interleukins; D007770:L-Lactate Dehydrogenase