The Cationic Cytokine IL-26 Differentially Modulates Virus Infection in Culture

Abstract

Interleukin-26 (IL-26) belongs to the IL-10 cytokine family, is produced by activated T cells, and targets epithelial target cells for signal transduction. Here, we describe the IL-26 effects on the infection of culture cells with recombinant vesicular stomatitis virus (VSV), human cytomegalovirus (HCMV), and herpes simplex virus type 1 (HSV-1) expressing green fluorescent protein. After pre-incubation with recombinant IL-26 and at low multiplicity of infection, VSV showed strongly enhanced infection and replication rates as measured for infectivity, for transcript levels, and for protein expression. Control proteins did not affect VSV infection. The IL-26 effect was independent of the IL-26 receptor and neutralized by anti-IL-26 serum. Pre-incubation of VSV was much more efficient than pre-incubation of the target cells to enhance virus infection. IL-26 increased virus adsorption to target cells as shown by quantitative reverse-transcription PCR. In contrast, the infection of IL-26-treated human fibroblasts with HCMV was inhibited and the infection by HSV-1 was not altered by IL-26. Thus, IL-26 differentially modulates the infection by different enveloped viruses.

Interleukin-26: An Emerging Player in Host Defense and Inflammation

“…In line with this, epithelial cells that constitute a first physical ‘barrier' against many viruses, do express IL-20R1 [11,26]. A recent study examined the role of IL-26 in viral infection models of epithelial cells [27].…”

IL-26 is overexpressed in chronically HCV-infected patients and enhances TRAIL-mediated cytotoxicity and interferon production by human NK cells

“…Although the expression of IL-26 by virus-transformed T cells suggested a role in antiviral immunity,17 25 its expression and role in viral infection remain poorly documented. We report that chronically HCV-infected patients exhibit high levels of circulating IL-26 and an accumulation in liver lesions.…”

“…The local accumulation of IL-26 may be related to its biochemical properties. Indeed, IL-26 has two clusters of basic amino acid, which can mediate its binding to glycosaminoglycans shared by proteoglycans on cell surfaces 25. One can suspect that IL-26, through its capacity to bind to glycosaminoglycans, accumulates in inflamed tissues and mediates, locally, the activation of newly recruited immune cells.…”

“…His 6 -tagged human IL-26 was expressed in Escherichia coli and purified as previously described 17 25…”

“…IL-10, IL-19, IL-20 and IFN-λ gene polymorphisms have been associated to susceptibility to HCV infection and/or response to treatment. Although the expression of IL-26 by virus-transformed T cells suggested a role in virus-associated immune responses,17 the expression and role of IL-26 in viral infections still remain poorly documented 17 25. In this study, we analysed the expression and potential role of IL-26 in patients chronically infected by HCV, an infection associated with a severe chronic inflammation.…”