Varicella-zoster virus infection induces the secretion of interleukin-8

Abstract

Interleukin-8 (IL-8) is an important mediator in neutrophil-mediated acute inflammation but has also a wide range of actions on various cells types. We demonstrated that infection of melanoma cells and fibroblasts with cell-associated varicella-zoster virus (VZV) and infection of a T cell line with cell-free VZV resulted in an induction of IL-8 secretion in vitro. The inhibition of the VZV replication with a drug interfering with its DNA replication had no effect on the IL-8 release. Since the IL-8 promoter contains binding sites for NF-kappaB and AP-1, melanoma cells and the T cell line were treated with inhibitors of NF-kappaB, JNK/SAPK or p38/MAPK prior to infection. In melanoma cells, the JNK/SAPK pathway was shown to be important for the IL-8 secretion during the VZV replication, whereas in the T cell line, not only the JNK/SAPK but also the p38/MAPK pathways were required for IL-8 secretion. The neutralisation of the IL-8 bioactivity had no significant consequence on the VZV replication, suggesting that IL-8 acts neither as a proviral nor as an antiviral cytokine during the VZV replication in vitro.

Parainfluenza Virus Type 1 Induces Epithelial IL-8 Production via p38-MAPK Signalling

“…Likewise, the presence of IL-8 in inflammatory infiltrates in lung tissues has been reported. Studies performed with different viruses have revealed that epithelial cells infected with specific viruses release IL-8 without requiring viral replication, as what occurs in RSV infections [18, 19]. Contact with the cellular receptor is sufficient to trigger IL-8 secretion, whereas other viruses only promote IL-8 synthesis during replication [21, 23].…”

“…It has been reported that epithelial cells, alveolar macrophages, and neutrophils secrete IL-8 [14–17]. Other authors have reported that infection with respiratory syncytial virus (RSV), varicella-zoster virus, and smallpox virus activates IL-8 secretion without viral replication [18, 19]. These observations indicate that the interaction between the virus and its receptor is sufficient to promote the signalling pathways that activate the IL-8 gene [20]; however, replication is necessary in other viruses, such as vaccinia virus and rhinovirus [21–23].…”

The clinical value of neutrophil extracellular traps

“…Currently, it is unclear whether severe pulmonary dysfunction or other diseases in conjunction with viral infections may be partly due to cf-DNA/NETs as a consequence of overwhelming inXammatory responses [46][47][48][49]. The hallmark of cystic Wbrosis is tenacious and purulent sputum, whose components include a complex of DNA, probably derived from NETs as well as elastase [50].…”

Varicella Zoster Virus Latency

“…The infected CD4 + T cells expressing skin homing factors transit to dermal endothelial cells, where the virus infects dermal fibroblasts and keratinocytes [27]. As the infection proceeds, cytokine-induced inflammation results in the formation of the characteristic varicella rash [28]. Within vesicular fluid, cell-free virus accumulates in sufficient amounts to distinguish vaccine from wild-type VZV as well to genotype the virus into one of the existing five circulating clades thus far identified [29–32].…”