Dataset Information

Human ?? T Cell Receptor Repertoires in Peripheral Blood Remain Stable Despite Clearance of Persistent Hepatitis C Virus Infection by Direct-Acting Antiviral Drug Therapy.

ABSTRACT: Human ?? T cells can contribute to clearance of hepatitis C virus (HCV) infection but also mediate liver inflammation. This study aimed to understand the clonal distribution of ?? T cells in peripheral blood of chronic HCV patients and following HCV clearance by interferon-free direct-acting antiviral drug therapies. To this end, ?? T cell receptor (TCR) repertoires were monitored by mRNA-based next-generation sequencing. While the percentage of V?9+ T cells was higher in patients with elevated liver enzymes and a few expanded V?3 clones could be identified in peripheral blood of 23 HCV-infected non-cirrhotic patients, overall clonality and complexity of ?? TCR repertoires were largely comparable to those of matched healthy donors. Monitoring eight chronic HCV patients before, during and up to 1?year after therapy revealed that direct-acting antiviral (DAA) drug therapies induced only minor alterations of TRG and TRD repertoires of V?9+ and V?9- cells. Together, we show that peripheral ?? TCR repertoires display a high stability (1) by chronic HCV infection in the absence of liver cirrhosis and (2) by HCV clearance in the course of DAA drug therapy.

SUBMITTER: Ravens S

PROVIDER: S-EPMC5864898 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Human γδ T Cell Receptor Repertoires in Peripheral Blood Remain Stable Despite Clearance of Persistent Hepatitis C Virus Infection by Direct-Acting Antiviral Drug Therapy.

Ravens Sarina S Hengst Julia J Schlapphoff Verena V Deterding Katja K Dhingra Akshay A Schultze-Florey Christian C Koenecke Christian C Cornberg Markus M Wedemeyer Heiner H Prinz Immo I

Frontiers in immunology 20180316

Human γδ T cells can contribute to clearance of hepatitis C virus (HCV) infection but also mediate liver inflammation. This study aimed to understand the clonal distribution of γδ T cells in peripheral blood of chronic HCV patients and following HCV clearance by interferon-free direct-acting antiviral drug therapies. To this end, γδ T cell receptor (TCR) repertoires were monitored by mRNA-based next-generation sequencing. While the percentage of Vγ9<sup>+</sup> T cells was higher in patients wit ...[more]

PMID: 29616028

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Project description:Hepatitis C virus (HCV) infection induces interferon (IFN)-stimulated genes (ISGs) and downstream innate immune responses. This study investigated whether baseline and on-treatment differences in these responses predict response versus virological breakthrough during therapy with direct-acting antivirals (DAAs). Thirteen HCV genotype 1b-infected patients who had previously failed a course of pegylated IFN/ribavirin were retreated with asunaprevir/daclatasvir for 24 weeks. After pretreatment biopsy, patients were randomized to undergo a second biopsy at week 2 or 4 on therapy. Microarray and NanoString analyses were performed on paired liver biopsies and analyzed using linear mixed models. As biomarkers for peripheral IFN responses, peripheral blood natural killer cells were assessed for phosphorylated signal transducer and activator of transcription 1 (pSTAT1) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) expression and degranulation. Nine of 13 (69%) patients achieved sustained virological response at 12 weeks off therapy (SVR12), and 4 experienced virological breakthroughs between weeks 4 and 12. Patients who achieved SVR12 displayed higher ISG expression levels in baseline liver biopsies and a higher frequency of pSTAT1 and TRAIL-expressing, degranulating natural killer cells in baseline blood samples than those who experienced virological breakthrough. Comparing gene expression levels from baseline and on-therapy biopsies, 408 genes (±1.2-fold, P < 0.01) were differentially expressed. Genes down-regulated on treatment were predominantly ISGs. Down-regulation of ISGs was rapid and correlated with HCV RNA suppression. Conclusion: An enhanced IFN signature is observed at baseline in liver and blood of patients who achieve SVR12 compared to those who experience a virological breakthrough; the findings suggest that innate immunity may contribute to clearance of HCV during DAA therapy by preventing the emergence of resistance-associated substitutions that lead to viral breakthrough during DAA therapy.

Dataset Information

Human ?? T Cell Receptor Repertoires in Peripheral Blood Remain Stable Despite Clearance of Persistent Hepatitis C Virus Infection by Direct-Acting Antiviral Drug Therapy.

Publications

Human γδ T Cell Receptor Repertoires in Peripheral Blood Remain Stable Despite Clearance of Persistent Hepatitis C Virus Infection by Direct-Acting Antiviral Drug Therapy.

Similar Datasets

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