Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

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

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

PROVIDER: PRJNA413169 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Similar Datasets

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

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

2017-10-05 | GSE104597 | GEO

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

Project description:ResultsFirst, in patients receiving two different combinations of DAAs, we found that DAAs induced not only rapid viral clearance, but also a re-setting of antiviral immune responses in the peripheral blood. Specifically, we see a rapid decline in the expression of genes associated with chronic IFN stimulation (IFIT3, USP18, IFIT1) as well as a rapid decline in genes associated with inflammation (IL1β, CXCL10, CXCL11) in the peripheral blood that precedes the complete removal of virus from the blood. Interestingly, this rapid reversal of innate immune activation was not seen in patients who successfully clear chronic HCV infection using IFN-based therapy. Next, using a novel humanized mouse model (Fah-/-RAG2-/-IL2rgnull-FRG), we assessed the changes that occur in the hepatic tissue following DAA treatment. DAA-mediated rapid HCV clearance resulted in blunting of the expression of proinflammatory responses while functionally restoring the RIG-I/MAVS axis in the liver of humanized mice.ConclusionsCollectively, our data demonstrate that the rapid viral clearance following treatment with DAAs results in the rebalancing of innate antiviral response in both the peripheral blood and the liver as well as enhanced antiviral signaling within previously infected hepatocytes.

| S-EPMC5645093 | biostudies-literature

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

TMT10plex HCV infection

Project description:TMT10plex global proteomics of HCV infected HuH7.5 cells or HCV infected humanized mouse livers. TMT channels were combined after labeling and separated off line with a highPH reverse phase fractionation into 24 fractions.

2019-01-31 | MSV000083382 | MassIVE

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

Gene expression profile at single cell level of virus-specific CD8+ T cells in subjects with past or current HCV infection.

Project description:CD8+ T cells play a central role in antiviral control. We used single cell RNA sequencing (scRNA-seq) to analyze the differences of HCV-specific CD8+ T cells isolated from subjects that are chronically infected by HCV, individuals that spontaneously resolved an acute HCV infection, and chronic HCV patients in treatment with direct-acting antiviral (DAA). We also profiled non-HCV virus-specific cells (CMV and FLU) to analyze the impact of HCV infection on the adaptive immune response.

2023-06-08 | GSE228763 | 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

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data