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Rapid reversal of innate immune dysregulation in blood of patients and liver of humanized mice with HCV following DAA therapy

ABSTRACT: Analysis of transcriptional changes in the peripheral blood of patients prior to and following DAA treatment of HCV infection

ORGANISM(S): Homo sapiens

PROVIDER: GSE104597 | GEO | 2017/10/05

SECONDARY ACCESSION(S): PRJNA413169

REPOSITORIES: GEO

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Rapid reversal of innate immune dysregulation in blood of patients and livers of humanized mice with HCV following DAA therapy.

Project description: Not available

| S-EPMC5645093 | biostudies-literature

Rapid reversal of innate immune dysregulation in blood of patients and liver of humanized mice with HCV following DAA therapy

Project description:Rapid reversal of innate immune dysregulation in blood of patients and liver of humanized mice with HCV following DAA therapy

| PRJNA413169 | ENA

Single-cell transcriptomic analyses of T cells in chronic HCV-infected patients dominated by DAA-induced interferon signaling changes

Project description:Chronic infection with HCV is manifested by dysregulation of innate immune responses and impaired T cell function at multiple levels. These changes may impact susceptibility to other infections, responsiveness to antiviral therapies, vaccine responsiveness, and development of complications such as hepatocellular carcinoma. Highly effective direct-acting antiviral (DAA) therapy has revolutionized the management of chronic HCV, with expected cure rates exceeding 95%. DAA treatment represents a unique opportunity to investigate to what extent elimination of viral replication and chronic antigen stimulation can restore immunologic phenotype. In this study we interrogated the global transcriptional profile of isolated peripheral blood T cells before, during and after IFN-free DAA therapy using single cell mRNA sequencing. Our results demonstrate that T cells mapped at single-cell resolution have dramatic transcriptomic changes early after initiation of DAA and many of these changes are sustained after completion of DAA therapy. Specifically, we see a significant reduction in transcripts associated with innate immune activation and interferon signaling such as ISG15, ISG20, IFIT3, OAS and MX1 in many different T cell subsets. Furthermore, we find an early upregulation of a gene involved in suppression of immune activation, DUSP1, in circulating T cells. Conclusion: This study provides the first in-depth transcriptomic analysis at the single-cell level of patients undergoing DAA therapy, demonstrating that IFN-free antiviral therapy in chronic HCV infection induces hitherto unrecognized shifts in innate immune and interferon signaling within T cell populations early, during, and long-term after treatment. The present study provides a rich data source to explore the effects of DAA treatment on bulk T cells.

2021-07-19 | GSE178756 | GEO

Rapid intrahepatic and peripheral blood HCV RNA decline and HCV-specific immune response increase during IFN-free DAA therapy in HCV treatment-naïve patients

Project description:Rapid intrahepatic and peripheral blood HCV RNA decline and HCV-specific immune response increase during IFN-free DAA therapy in HCV treatment-naïve patients

| PRJNA451109 | ENA

Memory-like HCV-specific CD8+ T cells retain a chronic scar after cure of chronic HCV infection

Project description:Investigation of phenotypical changes between exhausted HCV-specific CD8+ T cells during chronic infection and after DAA-mediated cure investigation of heterogeneity withhin the HCV-specific CD8+ T cell population

2020-09-08 | GSE150305 | GEO

Memory-like HCV-specific CD8+ T cells retain a molecular scar after cure of chronic HCV infection

2020-09-07 | GSE150345 | GEO

Rapid intrahepatic and peripheral blood HCV RNA decline and HCV-specific immune response increase during IFN-free DAA therapy in HCV treatment-naïve patients [exp2]

Project description:Over 12 weeks of treatment with a combination of sofosbuvir, simeprevir and daclatasvir, PBMCs from 9 chronically HCV infected patients were profiled longitudinally (baseline, day 2, week 1, end of treatment (EOT) and post-treatment follow-up week 24)

2021-04-20 | GSE113420 | GEO

Rapid intrahepatic and peripheral blood HCV RNA decline and HCV-specific immune response increase during IFN-free DAA therapy in HCV treatment-naïve patients [exp1]

Project description:Over 12 weeks of treatment with a combination of sofosbuvir, simeprevir and daclatasvir, FNABs from 9 chronically HCV infected patients were profiled longitudinally (baseline, day 2, week 1, end of treatment (EOT) and post-treatment follow-up week 24)

2021-04-20 | GSE113419 | GEO

Rapid intrahepatic and peripheral blood HCV RNA decline and HCV-specific immune response increase during IFN-free DAA therapy in HCV treatment-naïve patients [exp1]

Project description:Rapid intrahepatic and peripheral blood HCV RNA decline and HCV-specific immune response increase during IFN-free DAA therapy in HCV treatment-naïve patients [exp1]

| PRJNA451112 | ENA

Rapid intrahepatic and peripheral blood HCV RNA decline and HCV-specific immune response increase during IFN-free DAA therapy in HCV treatment-naïve patients [exp2]

Project description:Rapid intrahepatic and peripheral blood HCV RNA decline and HCV-specific immune response increase during IFN-free DAA therapy in HCV treatment-naïve patients [exp2]

| PRJNA451113 | ENA

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