Department of Pathology, Immunology and Laboratory Medicine, University of Florida College of Medicine, Gainesville, FL 32610-0275, USA.
J Viral Hepat. 2010 Nov;17(11):757-69. doi: 10.1111/j.1365-2893.2009.01231.x.
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.
本研究旨在探讨细胞培养体系中丙型肝炎病毒（HCV）对单核细胞来源树突状细胞（DC）的反应。用转染的 Huh 7.5 细胞产生的不同滴度的 JFH-1（HCV 基因型 2a）或与新城疫病毒（NDV）共孵育，孵育贴壁衍生的 DC。通过实时逆转录聚合酶链反应、光镜观察形态和流式细胞术检测免疫表型评估感染和 I 型干扰素（IFN）反应。我们的数据表明，HCV 感染后 DC 中没有病毒复制或颗粒释放。与对照单核细胞相比，HCV 培养时单核细胞向未成熟 DC 转化的趋势更为明显。这种转变通过流式细胞术得到证实，似乎与病毒滴度有关。未成熟 DC 的数量也增加了。HCV 感染诱导 DC 中 IFNβ 的表达，数量似乎与病毒滴度呈负相关，表明 HCV 具有负调控此类细胞的能力。然而，IFNα似乎不受与病毒直接接触的影响。NDV 在 DC 中诱导的强烈 IFNβ 信号被 HCV 大大减弱。HCV 可负向影响 DC 的成熟并抑制 DC 的 I 型 IFN 反应。我们的研究结果表明了病毒逃避宿主免疫的一种机制。
