Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Comparison of immune restoration in early versus late alpha interferon therapy against hepatitis C virus.

ABSTRACT: Early alpha interferon (IFN-alpha) therapy against hepatitis C virus (HCV) rescues polyfunctional, virus-specific memory CD8(+) T cells, but whether immune restoration is possible during late therapy remains controversial. We compared immune restoration of HCV-specific memory T cells in patients who cleared HCV infection spontaneously and following early or late IFN therapy. Multifunctional CD4(+) and CD8(+) memory T cells were detected in spontaneous resolvers and in individuals treated early following an acute infection. In contrast, limited responses were detected in patients treated during chronic infection, and the phenotype of HCV-specific cells was influenced by autologous viral sequences. Our data suggest that irreversible damage to the HCV-specific memory T-cell response is associated with chronic HCV infection.

SUBMITTER: Abdel-Hakeem MS

PROVIDER: S-EPMC2937796 | biostudies-literature | 2010 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Comparison of immune restoration in early versus late alpha interferon therapy against hepatitis C virus.

Abdel-Hakeem Mohamed S MS Bédard Nathalie N Badr Gamal G Ostrowski Mario M Sékaly Rafick P RP Bruneau Julie J Willems Bernard B Heathcote E Jenny EJ Shoukry Naglaa H NH

Journal of virology 20100728 19

Early alpha interferon (IFN-alpha) therapy against hepatitis C virus (HCV) rescues polyfunctional, virus-specific memory CD8(+) T cells, but whether immune restoration is possible during late therapy remains controversial. We compared immune restoration of HCV-specific memory T cells in patients who cleared HCV infection spontaneously and following early or late IFN therapy. Multifunctional CD4(+) and CD8(+) memory T cells were detected in spontaneous resolvers and in individuals treated early f ...[more]

PMID: 20668076

Similar Datasets

Antiviral potency analysis and functional comparison of consensus interferon, interferon-alpha2a and pegylated interferon-alpha2b against hepatitis C virus infection.

Project description:BackgroundCurrent treatments for chronic hepatitis C virus (HCV) employing pegylated interferon (PEG-IFN) plus ribavirin are successful in approximately 50% of patients. Consensus IFN (CIFN) is a recombinant type I IFN that has demonstrated efficacy where conventional therapy has failed. We evaluated the host cell antiviral response and anti-HCV actions induced by IFN-alpha2a, PEG-IFN-alpha2b or CIFN on cultured immortalized human hepatocytes, Huh7 human hepatoma cells and Huh7 cells that harboured genetically distinct HCV RNA replicons or were infected with HCV 2a.MethodsCultured cells were treated with each IFN at relevant dosing based upon the pharmacological attainable in vivo serum maximum IFN concentrations. Gene expression and antiviral properties were measured using protein, RNA and virus quantification assays.ResultsCIFN treatment maximally triggered Janus kinase signal transducer and activator of transcription signalling in association with enhanced IFN-stimulated gene (ISG) expression. Increased antiviral potency of CIFN was associated with enhancement of IFN-induced blockade upon viral protein synthesis, protection of the cellular IFN promoter stimulator-1 (IPS-1) protein from HCV proteolysis and reduced replication of an IFN-resistant HCV replicon variant. Microarray analyses revealed that CIFN treatment induced a distinct pattern of ISG expression in cultured hepatocytes compared with other IFNs.ConclusionsCIFN exhibits increased anti-HCV potency over IFN-alpha2a and PEG-IFN through maximal and distinct induction of ISG expression and enhanced intracellular innate antiviral response, while protecting IPS-1 from HCV proteolysis. CIFN might offer a treatment regimen imparting translational control programmes and restoration of the retinoic acid-inducible gene-1/IPS-1 pathway and could be considered for previous treatment failures.

| S-EPMC2884366 | biostudies-literature

Comparison of Compliance and Efficacy of Pegylated Interferon α-2a and α-2b in Adults with Chronic Hepatitis C.

Project description:This study compares treatment completion rates and outcomes in hepatitis C virus (HCV) patients between those aged <60 and ≥60 years receiving pegylated interferon (PEG-IFN) α-2a or α-2b combined with ribavirin. No significant differences were found in treatment completion rates and virological responses between age-stratified patients or between genotype-stratified patients receiving PEG-IFN α-2a versus PEG-IFN α-2b. Significantly more patients ≥60 years of receiving PEG-IFN α-2b exhibited an early virological response compared to those receiving PEG-IFN α-2a (P = 0.002); for patients <60 years of age, treatment outcomes were similar between the 2 groups. More liver fibrosis was observed in patients with HCV of genotype 1 than in those with genotypes 2 or 3. Mean changes in pre- and post-treatment fibrosis variables (bilirubin, platelet count, liver enzymes, FIB-4, and APRI) in HCV genotype 1 patients were greater in those receiving PEG-IFN α-2b than in those receiving PEG-IFN α-2a. Significant differences were not observed between age- and HCV genotype-stratified patients receiving PEG-IFN α-2a and -α-2b, but α-2b appears to have a modest efficacy advantage over α-2b, particularly in male HCV patients ≥60 years of age.

| S-EPMC6479237 | biostudies-literature

Antiviral Activity of Interferon Alpha-Inducible Protein 27 Against Hepatitis B Virus Gene Expression and Replication.

Project description:Despite the availability of effective vaccines, hepatitis B virus (HBV) is still a major health issue, and approximately 350 million people have been chronically infected with HBV throughout the world. Interferons (IFNs) are the key molecules in the innate immune response that restrict several kinds of viral infections via the induction of hundreds of IFN-stimulated genes (ISGs). The objective of this study was to confirm if interferon alpha-inducible protein 27 (IFI27) as an ISG could inhibit HBV gene expression and DNA replication both in cell culture and in a mouse model. In human hepatoma cells, IFI27 was highly induced by the stimulation of IFN-alpha (IFN-α), and it potentiated the anti-HBV activity. The overexpression of IFI27 inhibited, while its silencing enhanced the HBV replication in HepG2 cell. However, the knocking out of IFI27 in HepG2 cells robustly increases the formation of viral DNA, RNA, and proteins. Detailed mechanistic analysis of the HBV genome showed that a sequence [nucleotide (nt) 1715-1815] of the EnhII/Cp promoter was solely responsible for viral inhibition. Similarly, the hydrodynamic injection of IFI27 expression constructs along with the HBV genome into mice resulted in a significant reduction in viral gene expression and DNA replication. In summary, our studies suggested that IFI27 contributed a vital role in HBV gene expression and replication and IFI27 may be a potential antiviral agent for the treatment of HBV.

| S-EPMC8044325 | biostudies-literature

Understanding early serum hepatitis D virus and hepatitis B surface antigen kinetics during pegylated interferon-alpha therapy via mathematical modeling.

Project description:There is little information on the early kinetics of hepatitis delta virus (HDV) and hepatitis B surface antigen (HBsAg) during interferon-? therapy. Here a mathematical model was developed and fitted to frequent HDV and HBsAg kinetic data from 10 patients during the first 28 weeks of pegylated-interferon-?2a (peg-IFN) therapy. Three patients achieved a complete virological response (CVR), defined as undetectable HDV 6 months after treatment stopped with loss of HBsAg and anti-HBsAg seroconversion. After initiation of therapy, a median delay of 9 days (interquartile range [IQR]: 5-15) was observed with no significant changes in HDV level. Thereafter, HDV declined in a biphasic manner, where a rapid first phase lasting for 25 days (IQR: 23-58) was followed by a slower or plateau second phase. The model predicts that the main effect of peg-IFN is to reduce HDV production/release with a median effectiveness of 96% (IQR: 93-99.8). Median serum HDV half-life (t1/2 ) was estimated as 2.9 days (IQR: 1.5-5.3) corresponding to a pretreatment production and clearance of about 10(10) (IQR: 10(9.7) -10(10.7) ) virions/day. None of the patients with flat second phase in HDV achieved CVR. HBsAg kinetics of decline paralleled the second phase of HDV decline consistent with HBsAg-productive-infected cells being the main source of production of HDV, with a median t1/2 of 135 days (IQR: 20-460). The interferon lambda-3 polymorphism (rs12979860) was not associated with kinetic parameters.Modeling results provide insights into HDV-host dynamics, the relationship between serum HBsAg levels and HBsAg-infected cells, IFN's mode of action, and its effectiveness. The observation that a flat second phase in HDV and HBsAg kinetics was associated with failure to achieve CVR provides the basis to develop early stopping rules during peg-IFN treatment in HDV-infected patients.

| S-EPMC4245461 | biostudies-literature

Interferon alpha treatment stimulates interferon gamma expression in type I NKT cells and enhances their antiviral effect against hepatitis C virus.

Project description:Interferon (IFN) inhibits hepatitis C virus (HCV) replication through up-regulation of intrahepatic IFN-stimulated gene expression but also through activation of host immune cells. In the present study, we analyzed the immune cell-mediated antiviral effects of IFN-α using HCV-infected mice. Urokinase-type plasminogen activator (uPA)-severe combined immunodeficiency (SCID) mice with transplanted human hepatocytes were infected with genotype 1b HCV and injected with human peripheral blood mononuclear cells (PBMCs). IFN-α treatment following human PBMC transplantation resulted in a significant reduction in serum HCV RNA titers and a higher human CD45-positive mononuclear cell chimerism compared to mice without human PBMC transplantation. In mice with human PBMCs treated with IFN-α, serum concentrations of IFN-γ increased, and natural killer T (NKT) cells, especially type I NKT cells, produced IFN-γ. Mice in which IFN-γ signaling was blocked using antibody or in which transplanted PBMCs were depleted for type I NKT cells showed similar levels of anti-HCV effect compared with mice treated only with IFN-α. These results show that IFN-α stimulates IFN-γ expression in type 1 NKT cells and enhances the inhibition of HCV replication. We propose that type 1 NKT cells might represent a new therapeutic target for chronic hepatitis C patients.

| S-EPMC5333814 | biostudies-literature

Parapneumonic pleural effusion: early versus late thoracoscopy.

Project description:To evaluate the best time to perform thoracoscopy for the treatment of complicated parapneumonic pleural effusion in the fibrinopurulent phase in patients ? 14 years of age, regarding the postoperative evolution and occurrence of complications.This was a retrospective comparative study involving patients with parapneumonic pleural effusion presenting with septations or loculations on chest ultrasound who underwent thoracoscopy between January of 2000 and January of 2013. The patients were divided into two groups: early thoracoscopy (ET), performed by day 5 of hospitalization; and late thoracoscopy (LT), performed after day 5 of hospitalization.We included 60 patients, 30 in each group. The mean age was 3.4 years; 28 patients (46.7%) were male; and 47 (78.3%) underwent primary thoracoscopy (no previous simple drainage). The two groups were similar regarding gender, age, weight, and type of thoracoscopy (p > 0.05 for all). There was a significant difference between the ET and the LT groups regarding the length of the hospital stay (14.5 days vs. 21.7 days; p < 0.001). There were also significant differences between the groups regarding the duration of fever in days; the total number of days from admission to the initiation of drainage; and the total number of days with the drain in place. Eight patients (13.6%) had at least one post-thoracoscopy complication, there being no difference between the groups. There were no deaths.Performing ET by day 5 of hospitalization was associated with shorter hospital stays, shorter duration of drainage, and shorter duration of fever, although not with a higher frequency of complications, requiring ICU admission, or requiring blood transfusion.

| S-EPMC5790662 | biostudies-other

Interferon-alpha responsible EPN3 regulates hepatitis B virus replication.

Project description:Hepatitis B virus (HBV) infection remains a major health problem worldwide, and the current antiviral therapy, including nucleoside analogs, cannot achieve life-long cure, and clarification of antiviral host immunity is necessary for eradication. Here, we found that a clathrin-binding membrane protein epsin3 (EPN3) negatively regulates the expression of HBV RNA. EPN3 expression was induced by transfection of an HBV replicon plasmid, and reduced HBV-RNA level in hepatic cell lines and murine livers hydrodynamically injected with the HBV replicon plasmid. Viral RNA reduction by EPN3 was dependent on transcription, and independent from epsilon structure of viral RNA. Viral RNA reduction by overexpression of p53 or IFN-α treatment, was attenuated by knockdown of EPN3, suggesting its role downstream of IFN-α and p53. Taken together, this study demonstrates the anti-HBV role of EPN3. The mechanism how it decreases HBV transcription is discussed.

| S-EPMC9354525 | biostudies-literature

The Functional and Antiviral Activity of Interferon Alpha-Inducible IFI6 Against Hepatitis B Virus Replication and Gene Expression.

Project description:Hepatitis B virus is an enveloped DNA virus, that infects more than three hundred and sixty million people worldwide and leads to severe chronic liver diseases. Interferon-alpha inducible protein 6 (IFI6) is an IFN-stimulated gene (ISG) whose expression is highly regulated by the stimulation of type I IFN-alpha that restricts various kinds of virus infections by targeting different stages of the viral life cycle. This study aims to investigate the antiviral activity of IFI6 against HBV replication and gene expression. The IFI6 was highly induced by the stimulation of IFN-α in hepatoma cells. The overexpression of IFI6 inhibited while knockdown of IFI6 elevated replication and gene expression of HBV in HepG2 cells. Further study determined that IFI6 inhibited HBV replication by reducing EnhII/Cp of the HBV without affecting liver enriched transcription factors that have significant importance in regulating HBV enhancer activity. Furthermore, deletion mutation of EnhII/Cp and CHIP analysis revealed 100 bps (1715-1815 nt) putative sites involved in IFI6 mediated inhibition of HBV. Detailed analysis with EMSA demonstrated that 1715-1770 nt of EnhII/Cp was specifically involved in binding with IFI6 and restricted EnhII/Cp promoter activity. Moreover, IFI6 was localized mainly inside the nucleus to involve in the anti-HBV activity of IFI6. In vivo analysis based on the hydrodynamic injection of IFI6 expression plasmid along with HBV revealed significant inhibition of HBV DNA replication and gene expression. Overall, our results suggested a novel mechanism of IFI6 mediated HBV regulation that could develop potential therapeutics for efficient HBV infection treatment.

| S-EPMC8047077 | biostudies-literature

Single-cell transcriptomics unveils multifaceted immune heterogeneity in early-onset versus late-onset cervical cancer.

Project description:Early-onset (EOCC) and late-onset cervical cancers (LOCC) represent two clinically distinct subtypes, each defined by unique clinical manifestations and therapeutic responses. However, their immunological profiles remain poorly explored. Herein, we analyzed single-cell transcriptomic data from 4 EOCC and 4 LOCC samples to compare their immune architectures. Epithelial cells in EOCC exhibited a notable dual immunological phenotype, characterized by immune-suppressive properties driven by elevated CXCL production, alongside immune-stimulatory features linked to heightened HLA molecule expression. CD4 + and CD8 + T cells in LOCC demonstrated a heightened activation state, while NK cells exhibited diminished cytotoxicity. Macrophages in LOCC displayed enhanced polarization towards both M1 and M2 phenotypes, along with dendritic cells showing augmented antigen-presenting capacity. Regarding cancer-associated fibroblasts (CAFs), EOCC was enriched with inflammatory CAFs, whereas LOCC harbored a higher proportion of antigen-presenting CAFs. These findings reveal the multifaceted immune heterogeneity between EOCC and LOCC, underscoring the imperative for age-tailored immunotherapeutic strategies.

| S-EPMC11730844 | biostudies-literature

Surgical management of severe pancreatic fistula after pancreatoduodenectomy: a comparison of early versus late rescue pancreatectomy.

Project description:BackgroundRescue pancreatectomy for postoperative pancreatic fistula (POPF) after pancreatoduodenectomy (PD) is associated with high mortality. However, in-depth literature is scarce and hard to interpret. This study aimed to evaluate the indications, timing and perioperative outcomes of rescue pancreatectomy for severe POPF after PD.MethodsRetrospective single-centre study from all consecutive patients (2008-2020) with POPF-C after PD (ISGPS 2016 definition). Major morbidity and mortality during hospitalization or within 90 days after index surgery were evaluated. Time from index surgery to rescue pancreatectomy was dichotomized in early and late (≤ 11 versus > 11 days).ResultsFrom 1076 PDs performed, POPF-B/C occurred in 190 patients (17.7%) of whom 53 patients (4.9%) with POPF-C were included. Mortality after early rescue pancreatectomy did not differ significantly compared to late rescue pancreatectomy (13.6% versus 35.3%; p = 0.142). Timing of a rescue pancreatectomy did not change significantly during the study period: 11 (IQR, 8-14) (2008-2012) versus 14 (IQR, 7-33) (2013-2016) versus 8 days (IQR, 6-11) (2017-2020) (p = 0.140). Over time, the mortality in patients with POPF grade C decreased from 43.5% in 2008-2012 to 31.6% in 2013-2016 up to 0% in 2017-2020 (p = 0.014). However, mortality rates after rescue pancreatectomy did not differ significantly: 31.3% (2008-2012) versus 28.6% (2013-2016) versus 0% (2017-2020) (p = 0.104).ConclusionsRescue pancreatectomy for severe POPF is associated with high mortality, but an earlier timing might favourably influence the mortality. Hypothetically, this could be of value for pre-existent vulnerable patients. These findings must be carefully interpreted considering the sample sizes and differences among subgroups by patient selection.

| S-EPMC9722879 | biostudies-literature

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