Hepatitis C virus infection induces autocrine interferon signaling by human liver endothelial cells and release of exosomes, which inhibits viral replication.
Hepatitis C virus infection induces autocrine interferon signaling by human liver endothelial cells and release of exosomes, which inhibits viral replication.
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丙型肝炎病毒感染诱导人肝内皮细胞的自分泌干扰素信号传导并释放外泌体，从而抑制病毒复制。
DOI：
10.1053/j.gastro.2014.10.040
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发表时间：
2015-02
期刊：
影响因子：
29.4
通讯作者：
Rosen HR
中科院分区：
文献类型：
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作者：
Giugliano S;Kriss M;Golden-Mason L;Dobrinskikh E;Stone AE;Soto-Gutierrez A;Mitchell A;Khetani SR;Yamane D;Stoddard M;Li H;Shaw GM;Edwards MG;Lemon SM;Gale M Jr;Shah VH;Rosen HR
Liver sinusoidal endothelial cells (LSECs) make up a large proportion of the non-parenchymal cells in the liver. LSECs are involved in induction of immune tolerance, but little is known about their functions during hepatitis C virus (HCV) infection. Primary human LSECs (HLSECs) and immortalized liver endothelial cells (TMNK-1) were exposed to various forms of HCV, including full-length transmitted/founder virus, sucrose-purified Japanese Fulminant Hepatitis-1 (JFH-1), a virus encoding a luciferase reporter, and the HCV-specific pathogen-associated molecular pattern molecules. Cells were analyzed by confocal immunofluorescence, immunohistochemical, and PCR assays. HLSECs internalized HCV, independent of cell–cell contacts; HCV RNA was translated but not replicated. Through pattern recognition receptors (TLR7 and retinoic acid inducible gene 1), HCV RNA induced consistent and broad transcription of multiple interferons (IFNs); supernatants from primary HLSECs transfected with HCV-specific pathogen-associated molecular pattern molecules increased induction of IFNs and IFN-stimulated genes in HLSECs. Recombinant type I and type III IFNs strongly up-regulated HLSEC transcription of interferon λ 3 (IFNL3) and viperin (RSAD2), which inhibit replication of HCV. Compared to CD8+ T cells, HLSECs suppressed HCV replication within Huh7.5.1 cells, also inducing IFN-stimulated genes in co-culture. Conditioned media from IFN-stimulated HLSECs induced expression of antiviral genes by uninfected primary human hepatocytes. Exosomes, derived from HLSECs following stimulation with either type I or type III IFNs, controlled HCV replication in a dose-dependent manner. Cultured HLSECs produce factors that mediate immunity against HCV. HLSECs induce self-amplifying IFN-mediated responses and release of exosomes with antiviral activity.
