Liver transcriptome profiles correlates with viral control during hepatitis B virus infection
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE65359 | GEO | 2016/03/31
SECONDARY ACCESSION(S): PRJNA273765
REPOSITORIES: GEO
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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. The transcriptomes of 83 chronic hepatitis B patients (22 immune tolerant, 50 immune clearance, and 11 inactive carrier state) were analyzed by performing microarray analysis of liver biopsies.KEGG pathway analysis showed that immune response genes and interferon-stimulated genes were up-regulated in the immune clearance phase. Although immune tolerant patients and inactive state carriers had significantly different serum viral loads, the hepatic transcriptomes of the two groups were largely similar and only significantly differed in the expression of 109 genes (p < 0.01). Thus, we hypothesized that some of the 109 genes may be involved in HBV control and identified genes of interest by performing systematic screening using specific siRNAs. We showed that silencing candidate genes such as EVA1A resulted in significantly increased viral replication. Conversely, overexpression of candidate genes suppressed virus replication. Conclusions: The immune related pathways were up-regulated in the immune clearance phase but not in the inactive carrier phase. A number of host genes unrelated to immune pathways were expressed in the inactive carrier phase and these may participate in the control of hepatitis B virus replication, resulting in low viral replication. This dataset is part of the TransQST collection.
2016-03-31 | E-GEOD-65359 | biostudies-arrayexpress
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.
2023-09-30 | GSE243367 | GEO
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 Eastern woodchuck (Marmota monax) is naturally infected with woodchuck hepatitis virus (WHV), a hepadnavirus closely related to the human hepatitis B virus (HBV). The woodchuck is used as an animal model for studying chronic hepatitis B (CHB) and HBV-associated hepatocellular carcinoma (HCC) in humans, but the lack of sequence information has hitherto precluded functional genomics analysis. To address this major limitation of the model, we report here the sequencing, assembly and annotation of the woodchuck transcriptome, together with the generation of custom woodchuck microarrays. Using this new platform, we characterized the transcriptional response to persistent WHV infection and WHV-induced HCC. This revealed that chronic WHV infection, like HBV, is associated with (i) a limited intrahepatic type I interferon response, (ii) intrahepatic induction of markers associated with T cell exhaustion, (iii) elevated levels of suppressor of cytokine signaling 3 (SOCS3) in the liver, and (iv) intrahepatic accumulation of neutrophils. Underscoring the translational value of the woodchuck model, this study also determined that WHV-induced HCC shares molecular characteristics with a subtype of human HCC with poor prognosis. Conclusion: Our data establish the translational value of the woodchuck model and provide new insights into immune pathways which may play a role either in the persistence of HBV infection or the sequelae of CHB. Custom microarrays, generated from sequences obtained in transcriptome sequencing of woodchuck liver and PBMCs, were used to examine non-tumor vs. tumor gene expression in liver samples obtained from animals chronically infected with WHV (n=13). Multiple technical replicates per woodchuck sample are included.
2012-04-10 | E-GEOD-36545 | biostudies-arrayexpress
Project description:The Eastern woodchuck (Marmota monax) is naturally infected with woodchuck hepatitis virus (WHV), a hepadnavirus closely related to the human hepatitis B virus (HBV). The woodchuck is used as an animal model for studying chronic hepatitis B (CHB) and HBV-associated hepatocellular carcinoma (HCC) in humans, but the lack of sequence information has hitherto precluded functional genomics analysis. To address this major limitation of the model, we report here the sequencing, assembly and annotation of the woodchuck transcriptome, together with the generation of custom woodchuck microarrays. Using this new platform, we characterized the transcriptional response to persistent WHV infection and WHV-induced HCC. This revealed that chronic WHV infection, like HBV, is associated with (i) a limited intrahepatic type I interferon response, (ii) intrahepatic induction of markers associated with T cell exhaustion, (iii) elevated levels of suppressor of cytokine signaling 3 (SOCS3) in the liver, and (iv) intrahepatic accumulation of neutrophils. Underscoring the translational value of the woodchuck model, this study also determined that WHV-induced HCC shares molecular characteristics with a subtype of human HCC with poor prognosis. Conclusion: Our data establish the translational value of the woodchuck model and provide new insights into immune pathways which may play a role either in the persistence of HBV infection or the sequelae of CHB. Custom microarrays, generated from sequences obtained in transcriptome sequencing of woodchuck liver and PBMCs, were used to examine liver gene expression in animals chronically infected with WHV (n=13), animals that had resolved WHV infection at least 12 months prior (R; n=11; range 12-18 months), and uninfected animals (U; n=10). Multiple technical replicates per woodchuck sample are included.
2012-04-10 | E-GEOD-36533 | biostudies-arrayexpress
Project description:The Eastern woodchuck (Marmota monax) is naturally infected with woodchuck hepatitis virus (WHV), a hepadnavirus closely related to the human hepatitis B virus (HBV). The woodchuck is used as an animal model for studying chronic hepatitis B (CHB) and HBV-associated hepatocellular carcinoma (HCC) in humans, but the lack of sequence information has hitherto precluded functional genomics analysis. To address this major limitation of the model, we report here the sequencing, assembly and annotation of the woodchuck transcriptome, together with the generation of custom woodchuck microarrays. Using this new platform, we characterized the transcriptional response to persistent WHV infection and WHV-induced HCC. This revealed that chronic WHV infection, like HBV, is associated with (i) a limited intrahepatic type I interferon response, (ii) intrahepatic induction of markers associated with T cell exhaustion, (iii) elevated levels of suppressor of cytokine signaling 3 (SOCS3) in the liver, and (iv) intrahepatic accumulation of neutrophils. Underscoring the translational value of the woodchuck model, this study also determined that WHV-induced HCC shares molecular characteristics with a subtype of human HCC with poor prognosis. Conclusion: Our data establish the translational value of the woodchuck model and provide new insights into immune pathways which may play a role either in the persistence of HBV infection or the sequelae of CHB. Custom microarrays, generated from sequences obtained in transcriptome sequencing of woodchuck liver and PBMCs, were used to examine kidney gene expression in animals chronically infected with WHV (n=5), animals that had resolved WHV infection at least 12 months prior (R; n=4; range 12-18 months), and uninfected animals (U; n=3). Multiple technical replicates per woodchuck sample are included.
2012-04-10 | E-GEOD-36541 | biostudies-arrayexpress
Project description:The Eastern woodchuck (Marmota monax) is naturally infected with woodchuck hepatitis virus (WHV), a hepadnavirus closely related to the human hepatitis B virus (HBV). The woodchuck is used as an animal model for studying chronic hepatitis B (CHB) and HBV-associated hepatocellular carcinoma (HCC) in humans, but the lack of sequence information has hitherto precluded functional genomics analysis. To address this major limitation of the model, we report here the sequencing, assembly and annotation of the woodchuck transcriptome, together with the generation of custom woodchuck microarrays. Using this new platform, we characterized the transcriptional response to persistent WHV infection and WHV-induced HCC. This revealed that chronic WHV infection, like HBV, is associated with (i) a limited intrahepatic type I interferon response, (ii) intrahepatic induction of markers associated with T cell exhaustion, (iii) elevated levels of suppressor of cytokine signaling 3 (SOCS3) in the liver, and (iv) intrahepatic accumulation of neutrophils. Underscoring the translational value of the woodchuck model, this study also determined that WHV-induced HCC shares molecular characteristics with a subtype of human HCC with poor prognosis. Conclusion: Our data establish the translational value of the woodchuck model and provide new insights into immune pathways which may play a role either in the persistence of HBV infection or the sequelae of CHB. Custom microarrays, generated from sequences obtained in transcriptome sequencing of woodchuck liver and PBMCs, were used to examine spleen gene expression in animals chronically infected with WHV (n=4), animals that had resolved WHV infection at least 12 months prior (R; n=4; range 12-18 months), and uninfected animals (U; n=2). Multiple technical replicates per woodchuck sample are included.
2012-04-10 | E-GEOD-36544 | biostudies-arrayexpress
Project description:The Eastern woodchuck (Marmota monax) is naturally infected with woodchuck hepatitis virus (WHV), a hepadnavirus closely related to the human hepatitis B virus (HBV). The woodchuck is used as an animal model for studying chronic hepatitis B (CHB) and HBV-associated hepatocellular carcinoma (HCC) in humans, but the lack of sequence information has hitherto precluded functional genomics analysis. To address this major limitation of the model, we report here the sequencing, assembly and annotation of the woodchuck transcriptome, together with the generation of custom woodchuck microarrays. Using this new platform, we characterized the transcriptional response to persistent WHV infection and WHV-induced HCC. This revealed that chronic WHV infection, like HBV, is associated with (i) a limited intrahepatic type I interferon response, (ii) intrahepatic induction of markers associated with T cell exhaustion, (iii) elevated levels of suppressor of cytokine signaling 3 (SOCS3) in the liver, and (iv) intrahepatic accumulation of neutrophils. Underscoring the translational value of the woodchuck model, this study also determined that WHV-induced HCC shares molecular characteristics with a subtype of human HCC with poor prognosis. Conclusion: Our data establish the translational value of the woodchuck model and provide new insights into immune pathways which may play a role either in the persistence of HBV infection or the sequelae of CHB.
2012-04-11 | GSE36545 | GEO
Project description:The Eastern woodchuck (Marmota monax) is naturally infected with woodchuck hepatitis virus (WHV), a hepadnavirus closely related to the human hepatitis B virus (HBV). The woodchuck is used as an animal model for studying chronic hepatitis B (CHB) and HBV-associated hepatocellular carcinoma (HCC) in humans, but the lack of sequence information has hitherto precluded functional genomics analysis. To address this major limitation of the model, we report here the sequencing, assembly and annotation of the woodchuck transcriptome, together with the generation of custom woodchuck microarrays. Using this new platform, we characterized the transcriptional response to persistent WHV infection and WHV-induced HCC. This revealed that chronic WHV infection, like HBV, is associated with (i) a limited intrahepatic type I interferon response, (ii) intrahepatic induction of markers associated with T cell exhaustion, (iii) elevated levels of suppressor of cytokine signaling 3 (SOCS3) in the liver, and (iv) intrahepatic accumulation of neutrophils. Underscoring the translational value of the woodchuck model, this study also determined that WHV-induced HCC shares molecular characteristics with a subtype of human HCC with poor prognosis. Conclusion: Our data establish the translational value of the woodchuck model and provide new insights into immune pathways which may play a role either in the persistence of HBV infection or the sequelae of CHB.
2012-04-11 | GSE36533 | GEO
Project description:The Eastern woodchuck (Marmota monax) is naturally infected with woodchuck hepatitis virus (WHV), a hepadnavirus closely related to the human hepatitis B virus (HBV). The woodchuck is used as an animal model for studying chronic hepatitis B (CHB) and HBV-associated hepatocellular carcinoma (HCC) in humans, but the lack of sequence information has hitherto precluded functional genomics analysis. To address this major limitation of the model, we report here the sequencing, assembly and annotation of the woodchuck transcriptome, together with the generation of custom woodchuck microarrays. Using this new platform, we characterized the transcriptional response to persistent WHV infection and WHV-induced HCC. This revealed that chronic WHV infection, like HBV, is associated with (i) a limited intrahepatic type I interferon response, (ii) intrahepatic induction of markers associated with T cell exhaustion, (iii) elevated levels of suppressor of cytokine signaling 3 (SOCS3) in the liver, and (iv) intrahepatic accumulation of neutrophils. Underscoring the translational value of the woodchuck model, this study also determined that WHV-induced HCC shares molecular characteristics with a subtype of human HCC with poor prognosis. Conclusion: Our data establish the translational value of the woodchuck model and provide new insights into immune pathways which may play a role either in the persistence of HBV infection or the sequelae of CHB.
2012-04-11 | GSE36544 | GEO