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Articles 1 - 4 of 4
Full-Text Articles in Medicine and Health Sciences
Human Ezrin-Moesin-Radixin Proteins Modulate Hepatitis C Virus Infection, Terence Bukong, Karen Kodys, Gyongyi Szabo
Human Ezrin-Moesin-Radixin Proteins Modulate Hepatitis C Virus Infection, Terence Bukong, Karen Kodys, Gyongyi Szabo
Gyongyi Szabo
Host cytoskeletal proteins of the ezrin-moesin-radixin (EMR) family have been shown to modulate single-stranded RNA virus infection through regulating stable microtubule formation. Antibody engagement of CD81, a key receptor for hepatitis C virus (HCV) entry, induces ezrin phosphorylation. Here we tested the role of EMR proteins in regulating HCV infection and explored potential therapeutic targets. We show that HCV E2 protein induces rapid ezrin phosphorylation and its cellular redistribution with F-actin by way of spleen tyrosine kinase (SYK). Therapeutically blocking the functional roles of SYK or F-actin reorganization significantly reduced Huh7.5 cell susceptibility to HCV J6/JFH-1 infection. Using gene regulation, …
Human Type 2 Myeloid Dendritic Cells Produce Interferon-Lambda And Amplify Interferon-Alpha In Response To Hepatitis C Virus Infection, Shuye Zhang, Karen Kodys, Kui Li, Gyongyi Szabo
Human Type 2 Myeloid Dendritic Cells Produce Interferon-Lambda And Amplify Interferon-Alpha In Response To Hepatitis C Virus Infection, Shuye Zhang, Karen Kodys, Kui Li, Gyongyi Szabo
Gyongyi Szabo
BACKGROUND and AIMS: The type III interferons (IFN-lambdas: interleukin [IL]-28a, IL-28b, and IL-29) have important roles in hepatitis C virus (HCV) infection, but little is understood about what cells produce these cytokines or how production is activated. We investigated whether human immune cells recognize HCV-infected cells and respond by producing IFN-lambda. METHODS: We cultured healthy human peripheral blood mononuclear cells (PBMCs) with different populations of immune cells and Japanese fulminant hepatitis-1 (JFH-1) HCV-infected Huh7.5 (cell culture-derived HCV particles [HCVcc]/Huh7.5) cells. RESULTS: Human PBMCs recognized HCVcc/Huh7.5 cells and responded by producing IFN-alpha, IFN-gamma, and IFN-lambda. A rare subset of myeloid dendritic …
Innate Immune Cell Networking In Hepatitis C Virus Infection, Banishree Saha, Gyongyi Szabo
Innate Immune Cell Networking In Hepatitis C Virus Infection, Banishree Saha, Gyongyi Szabo
Gyongyi Szabo
Persistent viral infection, such as HCV infection, is the result of the inability of the host immune system to mount a successful antiviral response, as well as the escape strategies devised by the virus. Although each individual component of the host immune system plays important roles in antiviral immunity, the interactive network of immune cells as a whole acts against the virus. The innate immune system forms the first line of host defense against viral infection, and thus, virus elimination or chronic HCV infection is linked to the direct outcome of the interactions between the various innate immune cells and …
Alcohol Facilitates Hcv Rna Replication Via Up-Regulation Of Mir-122 Expression And Inhibition Of Cyclin G1 In Human Hepatoma Cells, Wei Hou, Terence Bukong, Karen Kodys, Gyongyi Szabo
Alcohol Facilitates Hcv Rna Replication Via Up-Regulation Of Mir-122 Expression And Inhibition Of Cyclin G1 In Human Hepatoma Cells, Wei Hou, Terence Bukong, Karen Kodys, Gyongyi Szabo
Gyongyi Szabo
BACKGROUND: Clinical studies demonstrate synergistic liver damage by alcohol and hepatitis C virus (HCV); however, the mechanisms by which alcohol promotes HCV infection remain obscure. The liver-specific microRNA-122 (miR-122) regulates HCV replication and expression of host genes, including Cyclin G1. Here, we hypothesized that alcohol regulates miR-122 expression and thereby modulates HCV RNA replication. METHODS: The J6/JFH/Huh-7.5 model of HCV infection was used in this study. Real-time quantitative polymerase chain reaction, Western blotting, electrophoretic mobility shift assay, and confocal microscopy were used for experimental analysis. RESULTS: We found that acute alcohol exposure (25 mM) significantly increased intracellular HCV RNA as …