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- Halasz, R, et al.
(författare)
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Relation between GB virus C/hepatitis G virus and fulminant hepatic failure may be secondary to treatment with contaminated blood and/or blood products
- 1999
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Ingår i: Gut. - : BMJ. - 0017-5749 .- 1468-3288. ; 44:2, s. 274-278
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Tidskriftsartikel (refereegranskat)abstract
- The role of the recently discovered GB virus C (GBV-C)/hepatitis G virus in fulminant hepatic failure (FHF) has been debated. Although GBV-C RNA has been detected in many cases of FHF, recent data suggest that the relation between GBV-C and FHF may be accidental.AimsTo retrospectively investigate the possible relation between the presence of GBV-C markers (RNA or antibodies to the GBV-C envelope 2 (E2) glycoprotein) and FHF.MethodsThe presence of GBV-C RNA was determined in serum samples from 58 patients diagnosed with FHF using a reverse transcriptase polymerase chain reaction. Amplified genetic fragments were directly sequenced by the dideoxy chain termination method. Antibodies to GBV-C in serum samples were detected by enzyme immunoassay based on a recombinant GBV-C E2 protein.ResultsNine (16%) patients with FHF had GBV-C RNA and 14 (24%) had GBV-C E2 antibodies, which are higher frequencies than in healthy subjects (p<0.01 and p<0.05 respectively). Seven of ten patients with GBV-C markers during FHF tested negative for these markers before therapy with blood and/or blood products. Sequence analysis of the GBV-C NS3 region fragments of six FHF patients showed no common sequence pattern or motif.ConclusionsThe frequencies of both GBV-C RNA and antibodies are higher in patients with FHF than in healthy subjects. However, these increased frequencies may in many cases be explained by the use of contaminated blood and/or blood products given as therapy.
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- Levander, S, et al.
(författare)
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Immune-mediated effects targeting hepatitis C virus in a syngeneic replicon cell transplantation mouse model
- 2018
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Ingår i: Gut. - : BMJ. - 1468-3288 .- 0017-5749. ; 67:8, s. 1525-1535
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Tidskriftsartikel (refereegranskat)abstract
- HCV is characterised by its ability to establish chronic infection in hepatocytes and to replicate in the presence of an inflammation. We mimicked this situation in vivo in immune-competent mice by syngeneic transplantation of HCV replicon-containing mouse hepatoma cells.DesignA total of 5 million H-2b positive Hep56.1D cells, carrying a subgenomic genotype (gt) 2a replicon (HCV replicon cells) or stably expressing comparable levels of the HCV NS3/4A protease/helicase complex (NS3/4A hepatoma cells), were injected subcutaneously into syngeneic H-2b-restricted mice. Kinetics of tumour growth, HCV RNA replication levels and HCV-specific immune responses were monitored. For immune monitoring, new H-2b-restricted cytotoxic T cell epitopes within the gt2a NS3/4A region were mapped. Immune mice were generated by DNA-based vaccination.ResultsHCV replicon and NS3/4A hepatoma cells generated solid tumours in vivo. Similar to what is seen in human HCV infection did HCV RNA replicate in the presence of inflammation. NS3/4A-specific CD8+ T cells seemed to transiently reduce HCV RNA levels. Both CD4+ and CD8+ T cells were required for protection against tumour growth. Vaccine-induced NS3/4A(gt2a)-specific T cells protected against HCV replicon tumours in wild-type, but not in HCV NS3/4A(gt1a)-transgenic mice with dysfunctional HCV-specific T cells. Importantly, as in human HCV infection, HCV replicon cells neither primed nor boosted a strong NS3/4A-specific T cell response.ConclusionSyngeneic transplantation of mouse HCV replicon cells into immune-competent animals mirrors many in vivo events in humans. This system is versatile and can be applied to any genetically modified H-2b-restricted mouse strain.
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- Lutckii, A, et al.
(författare)
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Evidence for B cell maturation but not trained immunity in uninfected infants exposed to hepatitis C virus
- 2020
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Ingår i: Gut. - : BMJ. - 1468-3288 .- 0017-5749. ; 69:12, s. 2203-2213
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Tidskriftsartikel (refereegranskat)abstract
- Vertical transmission of hepatitis C virus (HCV) is rare compared with other chronic viral infections, despite that newborns have an immature, and possibly more susceptible, immune system. It further remains unclear to what extent prenatal and perinatal exposure to HCV affects immune system development in neonates.DesignTo address this, we studied B cells, innate immune cells and soluble factors in a cohort of 62 children that were either unexposed, exposed uninfected or infected with HCV. Forty of these infants were followed longitudinally from birth up until 18 months of age.ResultsAs expected, evidence for B cell maturation was observed with increased age in children, whereas few age-related changes were noticed among innate immune cells. HCV-infected children had a high frequency of HCV-specific IgG-secreting B cells. Such a response was also detected in some exposed but uninfected children but not in uninfected controls. Consistent with this, both HCV-exposed uninfected and HCV-infected infants had evidence of early B cell immune maturation with an increased proportion of IgA-positive plasma cells and upregulated CD40 expression. In contrast, actual HCV viraemia, but not mere exposure, led to alterations within myeloid immune cell populations, natural killer (NK) cells and a distinct soluble factor profile with increased levels of inflammatory cytokines and chemokines.ConclusionOur data reveal that exposure to, and infection with, HCV causes disparate effects on adaptive B cells and innate immune cell such as myeloid cells and NK cells in infants.
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