Abstract
Hepatitis C virus (HCV) is a serious global health threat and current medical treatment options are limited. Interferon (IFN)-γ is an important proinflammatory cytokine with antiviral activity. However, the mechanism of IFN-γ in anti-HCV infection remains unclear. In this study, we investigated the role of IFN-γ on HCV infection of polarized Caco-2 cells using cell culture–derived HCV (HCVcc). We found that downregulation of claudin-1 (CLDN1) induced by IFN-γ resulted in disruption of barrier function as demonstrated by measurement of transepithelial electrical resistance and dextran permeability. Further, results from confocal microscopy and Western blot analysis showed that in addition to the reduction of CLDN1 expression, IFN-γ treatment also led to significant changes in the distribution of CLDN1, CD81, and scavenger receptor class B type I. Moreover, infection assays revealed that IFN-γ–treated cells showed decreased susceptibility to HCVcc infection. These results suggest a novel mechanism that IFN-γ may inhibit HCV infection by regulating CLDN1 expression and distribution of HCV receptors.
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