Hepatitis C virus modulates human monocyte-derived dendritic cells

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Abstract
Summary. This study is to examine the monocyte‐derived dendritic cell (DC) response to hepatitis C virus (HCV) in a cell culture system. Adherence‐derived DCs were incubated with various titres of JFH‐1 (HCV genotype 2a), generated from transfected Huh 7.5 cells or co‐incubated with Newcastle disease virus (NDV). Infection and the type 1 interferon (IFN) response were assessed by real‐time reverse transcriptase‐polymerase chain reaction, morphology by light microscopy and immunophenotype by flow cytometry. Our data demonstrated no viral replication or particle release from DC after HCV infection. Morphologically, monocytes showed a tendency to shift to immature DCs when cultured with HCV, when compared with control monocytes. This shift was confirmed by flow cytometry and appeared to be related to viral titres. There was also an increase in immature DC numbers. HCV infection induced IFNβ expression in DCs, and the amount seemed to be inversely correlated with viral titres indicating that HCV has the capacity to negatively regulate such cells. However, IFNα does not appear to be affected by direct contact with the virus. A strong IFNβ signal induced by NDV in DC was substantially diminished by HCV. HCV negatively affects the maturation of DCs and suppresses the type 1 IFN response of DC. Our results suggest a mechanism of viral evasion of host immunity.

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