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Analyse des propriétés antivirales de l’interleukine-26

Abstract : Initially identified as a molecule over expressed in virus-transformed human T cells, IL-26 has been classified as a pro inflammatory cytokine due to its capacity to induce inflammatory cytokines production by myeloid and epithelial cells. Nevertheless, its biological functions remain largely unknown, in part because of its absence of orthologs in rat and mouse.Our team has previously reported that IL-26, overexpressed in HCV-infected patients, activates NK cells, rendering them able to kill HCV-infected hepatocytes. Results also showed that IL-26 accumulates in hepatocytes of HCV-infected patients, a localization that is not usual for a cytokine. This observation led us to evaluate whether IL-26 may exhibit non-conventional properties. In this study, we demonstrate that IL-26 protects in vitro hepatocytes from HCV infection. Confocal microscopy revealed that IL-26 colocalizes with viral dsRNA. This direct antiviral activity appears to rely on the capacity of IL-26 to bind to viral RNA and to inhibit its replication. Moreover, we investigated the capacity that IL-26 complexed to viral RNA could trigger an antiviral response by immune cells. Collectively, results show that IL-26 may have a manifold protective role during HCV infection: (i) an indirect role via its capacity to confer NK cell the capacity to kill HCV-infected cells, (ii) a direct role through its ability to inhibit viral replication, and (iii) a stimulatory role by rendering viral DNA inflammatory.
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Vincent Larochette. Analyse des propriétés antivirales de l’interleukine-26. Médecine humaine et pathologie. Université d'Angers, 2018. Français. ⟨NNT : 2018ANGE0041⟩. ⟨tel-02955501⟩

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