Differential Immune Transcriptomic Profiles between Vaccinated and Resolved HCV Reinfected Subjects
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE206397 | GEO | 2022/10/25
REPOSITORIES: GEO
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Project description:Differential Immune Transcriptomic Profiles between Vaccinated and Resolved HCV Reinfected Subjects
| PRJNA850425 | ENA
Project description:Successive episodes of hepatitis C virus (HCV) infection represent a unique natural rechallenge experiment to define correlates of long-term protective immunity and inform vaccine development. We applied a systems immunology approach to characterize longitudinal changes in the peripheral blood transcriptomic signatures in eight subjects who spontaneously resolved two successive HCV infections. Furthermore, we compared these signatures with those induced by an HCV T cell-based vaccine regimen. We identified a plasma cell transcriptomic signature during early acute HCV reinfection. This signature was absent in primary infection and following HCV vaccine boost. Spontaneous resolution of HCV reinfection was associated with rapid expansion of glycoprotein E2-specifc memory B cells in three subjects and transient increase in E2-specific neutralizing antibodies in six subjects. Concurrently, there was an increase in the breadth and magnitude of HCV-specific T cells in 7 out of 8 subjects. These results suggest a cooperative role for both antibodies and T cells in clearance of HCV reinfection and support the development of next generation HCV vaccines targeting these two arms of the immune system.
| S-EPMC9707775 | biostudies-literature
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
Project description:Hepatitis C virus (HCV) remains a significant public health threat as new 1.75 million HCV infections emerged worldwide. The majority of these infections become persistently infected, while around 30 % spontaneously eliminate the virus. Clinical factors for viral clarification are related to HCV interaction with host immune system, but little is known about the consequences after HCV spontaneous resolution. These individuals are difficult to recruit and study as acute infection is usually asymptomatic, and they will not be identified unless it progress to chronic infection. The study of peripheral blood mononuclear cells (PBMCs) of these patients is crucial, as PBMCs are one of the main HCV extrahepatic reservoirs, and its transcriptional profile provide us information of innate and adaptive immune response against HCV infection. Our research shows novel insight on molecular consequences of spontaneous resolution after an acute HCV infection. 96 Individuals with different HCV exposure status were recruited: spontaneous resolved, chronic infected and healthy controls; and the microRNA profile of their PBMCs were analyzed. Our results indicate similar disruption of miRNA expression on HCV chronic patients and those who spontaneously clarified the infection, compared to control patients. The disrupted miRNAs formed a signature of 21 miRNAs that mainly regulate lipid metabolism. This is the first report showing miRNA profile similarities between chronic HCV patients and spontaneous resolved individuals. Thus, our results suggest that HCV infection promotes molecular alterations in PBMCs that will last longer after HCV spontaneous eradication. This evidences open up new prospects in the management of individuals who spontaneously clarified infection, as they should be monitored and followed to dismiss future HCV-related complications, such us liver diseases complications. The identified miRNA signature could be used as biomarker to monitor HCV fingerprint on HCV-exposed patients.
2019-06-21 | E-MTAB-8023 | biostudies-arrayexpress
Project description:Early appearance of neutralizing antibodies during acute hepatitis C virus (HCV) infection is associated with spontaneous viral clearance. However, the longitudinal changes in antigen-specific memory B cell (MBC) responses associated with divergent HCV infection outcomes remain undefined. We characterized longitudinal changes in E2 glycoprotein-specific MBCs from subjects that either spontaneously resolved acute HCV infection or progressed to chronic infection using single cell RNA-seq and functional assays. HCV-specific antibodies in plasma from chronically infected subjects recognized multiple E2 genotypes, while those from spontaneous resolvers exhibited variable cross-reactivity to heterotypic E2. E2-specific MBCs from spontaneous resolvers peaked early after infection (4–6 months), following expansion of activated circulating T follicular helper cells (cTfh) expressing interleukin 21. In contrast, E2-specific MBCs from chronically infected subjects, enriched in VH1-69, expanded during persistent infection (> 1 year), in the absence of activated cTfh expansion. Early E2-specific MBCs from spontaneous resolvers produced monoclonal antibodies (mAbs) with fewer somatic hypermutations and lower E2 binding but similar neutralization as mAbs from late E2-specific MBCs of chronically infected subjects. These findings indicate that early cTfh activity accelerates expansion of E2-specific MBCs during acute infection, which might contribute to spontaneous clearance of HCV.
2021-10-24 | GSE157447 | GEO
Project description:HCV-specific CD8 cells are deeply exhausted in chronic hepatitis C and their function can only be partially corrected by modulation of up-regulated inhibitory pathways, suggesting a more complex molecular interplay. With the aim of identifying more suitable molecular targets to correct T cell dysfunction, we compared the transcriptome profile of HCV-specific CD8 cells of acute and chronic patients with the reference profile of HCV- and Flu-specific CD8 cells from patients able to resolve HBV infection spontaneously and from healthy subjects. First, the gene-expression profile of HCV-specific CD8 T cells from patients with chronically-evolving acute infection, that correspond to early but not established T exhausted cells, is consistent with a substantial functional impairment at the energetic and metabolic levels that leads to the accumulation of reactive oxygen species that contributes to the activation of stress sensor signaling pathways. A specific inhibition of the hyperactivated signaling downstream effectors elicits a functional metabolic T cell reconstitution in the majority of the tested patients early during HCV infection. Second, a predominant feature of late exhausted HCV specific T cells is a global downregulation of gene expression that affects multiple core processes, ranging from proteasome-dependent protein turnover to DNA repair, transcription, metabolism and cell cycle, that is presumably a consequence of precocious and dysregulated activity of histone methyltransferases (e.g. G9a and EZH2 HMTs). Third, a functional inhibition of HMTs leads to a T cell function reconstitution both as anti-viral cytokine production and as proliferative capacity and to a metabolic restoration specifically for late exhausted CD8 T cells with a strongly preferential effect on HCV-specific T cells. Virus-specific CD8+ T cells were isolated and sorted from early acute self-limited (5 patients), early chronic (8 patients), late resolved (4 patients), late chronic (7 patients) and from five healthy donors. RNA from sorted CD8+ T cells was processed, amplified, labeled, and hybridized to Agilent microarrays.
2019-03-01 | GSE111449 | GEO
Project description:The role of chronic hepatitis C virus (HCV) in the pathogenesis of HCV-associated hepatocellular carcinoma (HCC) is not completely understood, particularly at the molecular level. We studied gene expression in normal, pre-malignant (cirrhosis), and tumor (HCC) liver tissues using Affymetrix GeneChips. Keywords: cross-sectional
2009-01-08 | GSE14323 | GEO
Project description:Most individuals exposed to hepatitis C virus (HCV) become persistently infected while a minority spontaneously eliminate the virus. Although early immune events influence infection outcome, the cellular composition, molecular effectors, and timeframe of the host response active shortly after viral exposure remain incompletely understood. Employing specimens collected from people who inject drugs (PWID) with high risk of HCV exposure, we utilized RNA-Seq to characterize immune function in peripheral blood before, during, and after acute HCV infection resulting in spontaneous resolution. Our results provide a detailed description of innate immune programs active in peripheral blood during acute HCV infection, which include prominent type I interferon and inflammatory signatures. Innate immune gene expression rapidly returns to pre-infection levels upon viral clearance. This innate response coincides with a decrease in B cell transcriptional signatures. These results represent the first longitudinal transcriptomic characterization of human immune function in acute HCV infection and identify several dynamically regulated features of the complex response to natural HCV exposure.
2018-08-29 | GSE119117 | GEO
Project description:We have carried out a longitudinal study of PBMC's miRNA profile in HIV/HCV coinfected patients (n=28) after HCV eradication with DAA and SVR achivement. HIV monoinfected patients (n=16) were used as control. Briefly, peripheral venous blood samples were collected in EDTA tubes, and PBMCs were isolated within the first 4 hours after extraction.Total RNA including miRNAs were isolated from PBMCs with the miRNeasy Mini kit (Qiagen). Quality and integrity were evaluated by the Bioanalyzer 2100 with Agilent RNA 6000 Nano kit (Agilent). Only those samples with RIN > 7.5 were sequenced. Small RNA library synthesis and sequencing were performed at Centre for Genomic Regulation (CRG) at Barcelona (Spain). Small RNA libraries were constructed with Illumina’s TruSeq Small RNA kit v.4 (Illumina) and 50nts (1x50) were sequenced in an Illumina HiSeq2500, with a single read approach.
2021-11-23 | E-MTAB-10566 | biostudies-arrayexpress
Project description:Hepatic complications of HCV infection, including fibrosis and cirrhosis are accelerated in HIV-infected individuals. Although liver biopsy remains the gold standard for staging HCV-associated liver disease, this test can result in serious complications and is subject to sampling error. These challenges have prompted a search for non-invasive methods for liver fibrosis staging. To this end, we compared serum proteome profiles at different stages of fibrosis in HIV/HCV co- and HCV mono-infected patients using SELDI-TOF MS.
2018-04-09 | PXD009007 | Pride