Project description:Human primary hepatocytes isolated from chimeric mice were infected with HBV for 7 days. The comprehensive changes of miRNA levels were determined by miRNA array. MicroRNA expression levels were compared in between control and HBV-replicating primary hepatocytes by 2K microRNA microarrays
Project description:Changes of mRNA expression levels in HBV-infected human primary hepatocytes and those cells treated with bionanocapsules containing microRNA-93.
Project description:Human primary hepatocytes isolated from chimeric mice were infected with HBV for 7 days. The comprehensive changes of mRNA levels were determined by mRNA array. Also, microRNA93 was delivered into those cells using bionanocapsules to determine the effects of rescue expression of miR93 in HBV replicating cells, because we found that miR93 expression level was downregulated in HBV-infected hepatocytes. mRNA expression levels were compared in among control cells, HBV-infected cells, miR93 delivered cells, and HBV-infected cells with miR93 delivered, by 25K mRNA arrays.
Project description:Human primary hepatocytes isolated from chimeric mice were infected with HBV for 7 days. The comprehensive changes of mRNA levels were determined by mRNA array. Also, microRNA93 was delivered into those cells using bionanocapsules to determine the effects of rescue expression of miR93 in HBV replicating cells, because we found that miR93 expression level was downregulated in HBV-infected hepatocytes.
Project description:Human primary hepatocytes isolated from chimeric mice were infected with HBV for 7 days. The comprehensive changes of miRNA levels were determined by miRNA array.
Project description:Hepatitis B virus (HBV) infection is a major health problem worldwide and chronically infected individuals are at high risk of developing cirrhosis and hepatocellular carcinoma (HCC). The molecular mechanisms whereby HBV causes HCC are largely unknown. By using a biologically relevant system of HBV infection of primary human hepatocytes (PHHs), we studied how HBV perturbs gene expressions and signaling pathways of infected hepatocytes, and whether these effects are relevant to productive HBV infection and HBV-associated HCC. Using a human growth factor antibody array, we first showed that HBV infection induced a distinct profile of growth factor production by PHHs, marked particularly by significantly lower levels of transforming growth factor (TGF)-β family of proteins in the supernatant. Transcriptome profiling next revealed multiple changes in cell proliferation and cell cycle control pathways in response to HBV infection. A human cell cycle PCR array validated deregulation of more than 20 gene associated with cell cycle in HBV-infected PHHs. Cell cycle analysis demonstrated that HBV-infected PHHs are enriched in the G2/M phase as compared to the predominantly G0/G1 phase of cultured PHHs. HBV proviral host factors, such as PPARA, RXRA and CEBPB, were up-regulated upon HBV infection and particularly enriched in cells at the G2/M phase. Together, these results support that HBV deregulates cell cycle control to render a cellular environment that is favorable for productive HBV infection. By perturbing cell cycle regulation of infected cells, HBV may coincidently induce a premalignant phenotype that predispose infected hepatocytes to subsequent malignant transformation.
Project description:Background and Aims: Recent identification of intracellular DNA sensing pathways and involvement in numerous diverse disease processes including viral pathogenesis and autoimmunity suggests a role for these processes in liver pathology. The presence of these pathways in the liver and their role in HBV infection is unknown. Methods: In order to characterize the role of DNA sensing pathways in the liver, we utilized in vitro models. Microarray was performed on DNA treated and HBV infected hepatoma primary human hepatocytes. Results: Here we show that HBV infection and foreign DNA results in a significant innate immune response characterized by the production of inflammatory chemokines. The goal of this study is to characterize the changes in gene expression triggered by HBV and foreign DNA in primary human hepatocytes. PHHs were infected with HBV (MO.I = 50) for 40 hours. PHHs were transfected with 1μg/mL of ISD/dsDNA90 for 12 or 24 hours. Three replicates were performed for each condition.
Project description:Based on our recently developed 5 chemicals-cultured primary human hepatocytes (5C-PHH) model that supports long-term HBV infection, we performed multiplexed quantitative analysis of temporal changes of host proteome and transcriptome on PHH cells infected by HBV for up to 4 weeks. We showed that metabolic-, complement-, cytoskeleton-, mitochondrial- and oxidation-related pathways were modulated at transcriptional or post-transcriptional levels during long-term HBV infection, which led to cytopathic effects and could be partially rescued by early rather than late nucleot(s)ide analogs (NAs) administration.
