Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA285918 | ENA |
REPOSITORIES: ENA
Similar Datasets
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.
2016-08-09 | E-GEOD-69590 | biostudies-arrayexpress
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.
2016-08-09 | GSE69590 | GEO
Project description:Hepatitis B virus (HBV) infection is a risk of developing fibrosis, cirrhosis, liver failure, and hepatocellular carcinoma. Although HBV elimination requires complete elimination of covalently closed circular DNA (cccDNA), its treatment has not been established. Interferon (IFN) -γ, a type ⅠⅠ IFN, is produced by intrahepatic cytotoxic T lymphocytes and has the noncytolytic antiviral potential. However, the mechanism by which IFN-γ regulates HBV infection in hepatocytes has not been fully elucidated. In this study, to replicate the HBV infection and monitor the amount of cccDNA, we developed an in vitro HBV infection assay system with primary hepatocytes and examined the molecules and signaling pathways. IFN-γ suppressed both HBV propagation and transcription to the same extent as IFN-α. RNA microarray analysis revealed that IFN-γ stimulation induced not only IFN-γ but also IFN-α signaling activation and regulated HBV cccDNA. Moreover, the HBV production was reduced by IFN-γ through JAK-STAT signaling and interferon stimulated genes such as OAS2 and APOBEC3G. Taken together, these results demonstrate that IFN-γ suppresses both HBV propagation and transcription by activating specific intracellular signaling pathways in hepatocytes and suggests the future application of this particular signaling pathways or genes for the complete elimination of HBV.
2019-10-01 | GSE132628 | GEO
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.
2018-08-08 | GSE118295 | GEO
Project description:HIV Stimulation Induces a Unique Innate Immune Response in Kupffer Cells
| PRJNA285919 | ENA
Project description:Hepatitis B virus (HBV) is a leading cause of liver-related diseases and mortality. However, immune mechanisms governing the phases of HBV infection remain elusive. Understanding molecular components in hepatitis immunosuppression and progression is essential for developing immunotherapies for functional cure of chronic HBV infection. Our integrative analysis of intrahepatic tissue and peripheral PBMC samples from patients with acute and chronic HBV infection using single-cell RNA sequencing (scRNA-seq) and TCR/BCR sequencing (scTCR/BCR-seq) revealed three distinct lineages of PBMC-derived intrahepatic T lymphocytes (hpCTLs): exhausted GZMK+PDCD1+, short-lived effector KLRG1+, and inactivated GZMB+PRF1+ hpCTLs. Key factors such as FasL/Fas-mediated cytotoxicity, CD28 co-stimulation, and exhaustion status were identified as determinants of hpCTL functionality. Liver-resident DC-SIGN+ macrophages were found to act as antigen-presenting cells that cross-prime hpCTLs in response to IL-2 or as suppressive macrophages by inhibiting T cell immunity through IL-10 and PD-L1 production and Treg recruitment. The intrahepatic core cellular network, including DC-SIGN+ macrophages, CSF1+ST2+ mast cells, AREG+ liver-resident NK cells, CD14+ hepatocytes, and CXCL13+ TFH, was observed to modulate immune tolerance, activation, and suppression in HBV infection. This study inferred the core cellular network involved in immune phenotype switching across different hepatitis B phases and suggested potential immunomodulatory strategies for treating chronic HBV infection.
2024-12-05 | GSE283471 | GEO
Project description:The same entry pathway is shared by HBV and HDV. Both viruses attach to hepatocytes via heparansulfate proteoglycan and utilize sodium taurocholate co-transporting polypeptide (NTCP) for a specifc entry. This specific entry step is inhibited by Myrcludex B, a 47-aa lipopeptide myristoylated at the N-terminus. Here we compared the cellular response in the gene expression level triggerred by both viruses. The microarray data shows that HBV infection leads to a silent response but HDV infection triggers high level of innate response such as inteferon-stimulated genes (ISG) expression. Moreover, the response depends on the hepatic cell lines used for infection. Compared to HepG2 cells, HuH7 can not induce ISG even infected by HDV. Abstract of manuscript: Background & aims: Hepatitis B virus (HBV) and D virus (HDV) co-infections cause the most severe form of viral hepatitis. HDV induces an innate immune response, but it is unknown how the host cell senses HDV and if this defense affects HDV replication. We aim to characterize interferon (IFN) activation by HDV, identify the responsible sensor and evaluate the effect of IFN on HDV replication. Methods: HDV and HBV susceptible hepatoma cell lines and primary human hepatocytes (PHH) were used for infection studies. Viral markers and cellular gene expression were analyzed at different time points after infection. Pattern recognition receptors (PRRs) required for HDV-mediated IFN activation and the impact on HDV replication were studied using stable knock-down or overexpression of the PRRs. Results: Microarray analysis revealed that HDV but not HBV infection activated a broad range of interferon stimulated genes (ISGs) in HepG2NTCP cells. HDV strongly activated IFN-β and IFN-λ in cell lines and PHH. HDV induced IFN levels remained unaltered upon RIG-I or TLR3 knock-down, but were almost completely abolished upon MDA5 depletion. Conversely, overexpression of MDA5 but not RIG-I and TLR3 in Huh7.5NTCP cells partially restored ISG induction. During long-term infection, IFN levels gradually diminished in both HepG2NTCP and HepaRGNTCP cell lines. MDA5 depletion had little effect on HDV replication despite dampening HDV-induced IFN response. Moreover, treatment with type I or type III IFNs did not abolish HDV replication. Conclusions: Active replication of HDV induces an IFN-β/λ response, which is predominantly mediated by MDA5. This IFN response and exogenous IFN treatment have only a moderate effect on HDV replication in vitro indicating the adaption of HDV replication to an IFN activated state.
2018-01-30 | GSE109824 | GEO
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.
2016-01-01 | GSE72068 | GEO
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.
2016-10-25 | E-GEOD-79089 | biostudies-arrayexpress
Project description:Studying hepatitis delta virus (HDV) and developing new treatments is hampered by the absence limited availability of small animal models. Here a description of a robust mouse model of HDV infection that mimics several important characteristics of the human disease is presented. HDV- and HBV-replication competent genomes were delivered to the mouse liver using adeno-associated viruses (AAV) (AAV-HDV and AAV-HBV). Viral load, antigen expression and genomes were quantified at different time points after AAV injection. Furthermore, liver pathology, genome editing, and the activation of the innate immune response were evaluated. AAV-HDV infection initiated HDV replication in mouse hepatocytes. Genome-editing was confirmed by the presence of small and large-HDV-antigens and sequencing. Viral replication was detected for 45 days, even after the AAV-HDV vector had almost disappeared. In the presence of HBV, HDV infectious particles were detected in serum. Furthermore, as observed in patients, co-infection was associated with the reduction of HBV antigen expression and the onset of liver damage that included the up/down-regulation of genes involved in the development of liver pathologies. HDV replication induced a sustained type-I IFN response, which was significantly reduced in immunodeficient mice and almost absent in MAVS-deficient mice. The animal model described here reproduces important characteristics of human HDV infection and provides a valuable tool for characterizing the viral infection and for developing new treatments. Furthermore, MAVS was identified as a main player in HDV detection and adaptive immunity was found to be involved in the amplification of the innate immune response.
2017-06-30 | GSE98342 | GEO