ABSTRACT: Genome-wide analysis of different response of hepatocytes and oval cells to hepatitis B virus expression during HBV-related hepatocarcinogenesis
Project description:Analysis of genetic changes of hepatocytes and oval cells induced by HBV. The hypothesis tested in the present study was that hepatic progenitor cells (oval cells) are the founder cells of hepatocellular carcinoma (HCC). Results provide important information of the different responses of hepatocytes and oval cells to HBV expression during HBV-related hepatocarcinogenesis, such as up- or down-regulated oncogenes,tumor suppressor genes and signaling pathways.Results also provide new insights into the biology of human HCC. Total RNA obtained from primary cultured hepatocytes and oval cells isolated from the healthy and HBV transgenic mice.
Project description:Analysis of genetic changes of hepatocytes and oval cells induced by HBV. The hypothesis tested in the present study was that hepatic progenitor cells (oval cells) are the founder cells of hepatocellular carcinoma(HCC). Results provide important information of the different responses of hepatocytes and oval cells to HBV expression during HBV-related hepatocarcinogenesis, such as up- or down-regulated oncogenes,tumor suppressor genes and signaling pathways.Results also provide new insights into the biology of human HCC.
Project description:Analysis of genetic changes of hepatocytes and oval cells induced by HBV. The hypothesis tested in the present study was that hepatic progenitor cells (oval cells) are the founder cells of hepatocellular carcinoma (HCC). Results provide important information of the different responses of hepatocytes and oval cells to HBV expression during HBV-related hepatocarcinogenesis, such as up- or down-regulated oncogenes,tumor suppressor genes and signaling pathways.Results also provide new insights into the biology of human HCC.
Project description:Hepatitis B virus (HBV) can integrate into the chromosomes of infected hepatocytes, contributing to the production of hepatitis B surface antigen (HBsAg) and to hepatocarcinogenesis. We performed spatial transcriptomics to investigate the intrahepatic cell heterogeneity and the spatial distribution of transcriptionally active HBV integration events in different phases of chronic HBV infection. Our analysis revealed that transcriptionally active HBV integration occurred in chronically HBV-infected patients in different phases, including those patients with HBsAg loss, and antiviral treatment was associated with a decreased number and extent of viral integrations.
Project description:We applied small RNA Solexa sequencing technology to identify microRNA expression in human liver samples from surgically removed liver tissues including three normal liver tissues (distal normal liver tissue of liver hemangioma), an hepatitis B virus (HBV)-infected liver, a severe chronic hepatitis B liver, two HBV-related hepatocellular carcinoma (HCC), an hepatitis C virus (HCV)-related HCC, and an HCC without HBV or HCV infection. All samples were collected with the informed consent of the patients and the experiments were approved by the ethics committee of Second Military Medical University, Shanghai, China. We investigated the miRNome in human normal liver and suggested some deregulated abundantly expressed microRNAs in HCC. center_name: National Key Laboratory of Medical Immunology & Institute of Immunology, Second Military Medical University, Shanghai, China. Examination of miRNome in human liver samples from surgically removed liver tissues including three normal liver tissues (distal normal liver tissue of liver hemangioma), an hepatitis B virus (HBV)-infected liver tissue, a severe chronic hepatitis B liver tissue, an HBV-related hepatocellular carcinoma (HCC) tissue and adjacent liver tissues of different regions,an HBV-related HCC tissue and adjacent liver tissue, an hepatitis C virus (HCV)-related HCC tissue and adjacent liver tissue, and an HCC without HBV or HCV infection and adjacent liver tissue. All 15 human liver tissue samples.
Project description:Hepatitis B virus (HBV) infection could cause hepatitis, liver cirrhosis and hepatocellular carcinoma. HBV-mediated pathogenesis is only partially understood, but X protein (HBx) reportedly possesses oncogenic potential. Exosomes are small membrane vesicles with diverse functions released by various cells including hepatocytes, and HBV harnesses cellular exosome biogenesis and export machineries for virion morphogenesis and secretion. Therefore, HBV infection might cause changes in exosome contents with functional implications for both virus and host. In this project, exosome protein content changes induced by HBV and HBx were quantitatively analyzed by SILAC/LC-MS/MS. Exosomes prepared from SILAC-labeled hepatoma cell line Huh-7 transfected with HBx, wildtype or HBx-null HBV replicon plasmids were analyzed by LC-MS/MS.
Project description:Hepatitis B virus (HBV) infection could cause hepatitis, liver cirrhosis and hepatocellular carcinoma. HBV-mediated pathogenesis is only partially understood, but X protein (HBx) reportedly possesses oncogenic potential. Exosomes are small membrane vesicles with diverse functions released by various cells including hepatocytes, and HBV harnesses cellular exosome biogenesis and export machineries for virion morphogenesis and secretion. Therefore, HBV infection might cause changes in exosome contents with functional implications for both virus and host. In this project, exosome protein content changes induced by HBV and HBx were quantitatively analyzed by SILAC/LC-MS/MS. Exosomes prepared from SILAC-labeled hepatoma cell line Huh-7 transfected with HBx, wildtype or HBx-null HBV replicon plasmids were analyzed by LC-MS/MS.
Project description:Hepatitis B virus (HBV) is known for its ability to interact with the host cell DNA methylation machinery. In HBV-infected hepatocytes, this interaction leads to chronic liver diseases, including hepatocellular carcinoma (HCC). We studied the extent of genomic changes induced by natural HBV infection in human primary hepatocytes. Transcriptome and methylome profiles were obtained at different time points post-infection to identify HBV-specific alterations. Although gene expression and DNA methylation do not directly correlate, they both seem to reflect the effect of cell culture and viral infection at different levels.These changes in the hepatocyte cellular program shed light on the initial events leading to HBV-associated liver diseases.
Project description:The natural history of chronic hepatitis B virus (HBV) infection could be divided in different phases by transaminase and HBV replication levels. However, it remains unknown how the intrahepatic transcriptomes in patients are correlated with the clinical phases. Here, we determined the intrahepatic transcriptomes of chronic hepatitis B patients and examined the role of specific groups of genes, including immune-related genes, in the control of hepatitis B virus infection.
Project description:Chronic hepatitis B, C and D virus (HBV, HCV, HDV) infections are leading causes of liver disease and cancer worldwide. Although these viruses differ markedly in their life cycle and genomic organization, they exclusively infect hepatocytes. Recently, the sodium taurocholate cotransporting polypeptide (NTCP) was identified as the first functional receptor for HBV and HDV. Here, we report that NTCP also facilitates HCV entry into human hepatocytes, by augmenting the bile acid-mediated repression of IFN-stimulated genes (ISGs), including IFITM2 and IFITM3, to increase the susceptibility of cells to HCV entry. Furthermore, an HBV-derived preS1 peptide, known to bind NTCP and to inhibit bile acid uptake and HBV infection, inhibits HCV entry by enhancing the expression of ISGs. Our study highlights NTCP as a novel player linking bile acid metabolism to the interferon response in hepatocytes and establishes a role for NTCP in the entry process of multiple hepatotropic viruses, via distinct mechanisms. Collectively, these findings enhance our understanding of hepatitis virus-host interactions and suggest NTCP as an attractive antiviral target for HBV/HCV co-infection. Transcriptome profiling by DNA microarray of Huh7.5.1 cells transduced to express NTCP.