Hepatitis C, Chronic ; immunology ; Humans

Hepatitis C virus (HCV) infection is a worldwide problem in terms of public health. It causes chronic hepatitis C in 60-80% of patients after acute hepatitis C. Chronic hepatitis C can progress to liver cirrhosis and hepatocellular carcinoma. In the present time, combination therapy of pegylated interferon-alpha and ribavirin is the standard therapy for hepatitis C, but it results in sustained virologic response only in 45-80% of treated patients. In addition, there is no available effective vaccine for HCV. To develop effective immunotherapy or preventive vaccine, understanding of the immune response against HCV is prerequisite. Among several components of immune system, T cells play a key role in the clearance of HCV and immunopathology during hepatitis C. In the study of HCV infection, however, the most important limiting factor is the absence of small animal model as only humans and chimpanzees can be infected by HCV. In this review, T cell response against HCV, which has been known from the studies of the HCV-infected patients and chimpanzees, will be discussed in several circumstances, including acute hepatitis C, chronic hepatitis C and recovered status from hepatitis C.
T-Lymphocytes/*immunology ; Humans ; Hepatitis C, Chronic/immunology ; Hepatitis C/*immunology ; Hepacivirus/immunology

Epitopes ; immunology ; Hepacivirus ; immunology ; Hepatitis C ; immunology ; Humans

Hepatitis C ; immunology ; pathology ; Immunity, Innate

In this study, three expression vectors encoding unmodified glycoproteins E1 and E2 from H77 (1a), Hebei (1b) and JFH1 (2a) strains were constructed to form pVRC-H77-E1E2, pVRC-HeBei-E1E2 and pVRC-JFH1-E1E2 expressing constructs. The protein expression was confirmed by immunofluorescene assay(IFA) and Western blot. The Lentiviral vector has the ability to package the cellular membrane into pseudo-particles. The plasmid expressing HCV E1-E2 glycoproteins in native form was co-transfected into 293FT cells with a lentiviral packaging plasmid (pHR'CMV delta R8.2)and a self-inactivated (SIN) transfer plasmid (pCS-CG) containing a reporter EGFP gene to produce infectious HCV pseudo-particles(pp). Flow cytometry assays showed that the HCVpp could infect Huh7 and Huh7-CD81, and the infectivity in Huh7-CD81 was about 2-3 times higher than that in Huh7 cells. Meanwhile, HCVpp could neither infect non-liver cells, for example, the 293 cells, nor HepG2 cell . Titration of HCVpp by p24 ELISA assay or infection assay showed that this HCVpp may contain 5-25 ng/mL p24 or 10(4)-10(5) TU (transducing unit)/ ml. An in vitro HCV neutralizing assays based on HCVpp (1a, 1b, 2a) were then established using AP33, a monoclone antibody with cross-neutralizing ability to different HCV strains. The neutralizing ability of the antibodies from HCV infected patients was further studied with this HCVpp system. In summary, three kinds of HCVpp (1a, 1b, 2a subtype) were successfully developed; In vitro HCV neutralizing assays based on HCVpp and SIN lentiviral system were established. This system paves a way for characterization of early steps of HCV infection (host tropisms, receptor binding, membrane fusion, et al. ) or screening anti-HCV drugs (such as inhibitor to virus entry). This system can be further applied to assess the human immune responses in HCV patients or evaluate HCV vaccine candidates.
Hepacivirus ; immunology ; Hepatitis C Antibodies ; immunology ; Hepatitis C, Chronic ; immunology ; Humans ; Neutralization Tests ; Viral Envelope Proteins ; immunology ; Virion ; immunology

To evaluate the clinical feasibility of the antibody titer against a chimeric polypeptide (named Core 518), in which a domain of Core and NS3 of hepatitis C virus (HCV) was fused, ELISA was performed in a total of 76 serum samples. Each serum was serially diluted using two-fold dilution method with distilled water into 10 concentrations. They were all positive for second generation anti-HCV assay (HCV EIA II; Abbott Laboratories). Genotyping RT-PCR, quantitative competitive RT-PCR, and RIBA (Lucky Confirm; LG Biotech) were also assayed. Anti-Core 518 antibody was detected in x 12800 or higher dilutions of sera from 35 of 43 chronic hepatitis C (81.4%) and nine of 16 hepatocellular carcinoma sera (56.3%), one of four cirrhosis (25%), 0 of four acute hepatitis C, and one of nine healthy isolated anti-HCV-positive subjects (p=0.0000). The anti-Core 518 antibody titers were well correlated with the presence of HCV RNA in serum (p=0.002). The anti-Core 518 antibody titers decreased significantly in nine of ten responders to IFN-alpha treatment. Monitoring anti-Core 518 titers may be helpful not only for differentiating the status of HCV infection among patients with various type C viral liver diseases, but also for predicting responses to IFN-alpha treatment.
Adult ; Aged ; Female ; Genotype ; Hepatitis C/immunology* ; Hepatitis C/drug therapy* ; Hepatitis C/diagnosis ; Hepatitis C/blood ; Hepatitis C Antibodies/immunology* ; Hepatitis C Antibodies/blood ; Hepatitis C Antigens/immunology* ; Hepatitis C-Like Viruses/immunology* ; Hepatitis C-Like Viruses/genetics ; Human ; Immunoblotting ; Interferon Alfa-2a/therapeutic use* ; Male ; Middle Age ; RNA, Viral/blood ; Recombinant Fusion Proteins/immunology ; Viral Core Proteins/immunology* ; Viral Nonstructural Proteins/immunology*

Hepatitis C ; immunology ; Humans ; Killer Cells, Natural ; immunology

OBJECTIVETo observe the effect of hepatitis virus B on the detection rate of core antigen of hepatitis virus C in sera of chronic hepatitis C patients.

METHODHCVcAg and HCV RNA in sera were detected in 88 patients with chronic hepatitis C and 62 patients co-infected with HCV and HBV. At the same time, HBV DNA and HBeAg in sera were detected in 62 patients infected with HCV and HBV. Then we analyzed the correlation between HCVcAg and HBeAg/HBV DNA. The detection rates of HCVcAg in 88 patients with chronic hepatitis C and 62 patients co-infected with HCV and HBV were 72.7% (64/88) and 38.7% (24/62), respectively (x2 = 17.358, P less than 0.01).

RESULTSThe detection rates of HCV RNA in 88 patients with chronic hepatitis C and 62 patients co-infected with HCV and HBV was 81.8% (72/88) and 53.2% (33/62)respectively (x2=20.110, P less than 0.01). In 62 patients infected with HCV and HBV, the detection rate of HCVcAg in HBeAg positive patients and HBeAg negative patients were 28.6% (12/42) and 60% (12/20), respectively (x2 = 7.547, P = 0.011). Moreover, the positive rates of HBV DNA in HBeAg positive patients and HBeAg negative patients were 42.9% (18/42) and 80% (16/20), respectively (P more than 0.05). The detection rates of HCVcAg in HBV DNA positive patients and HBV DNA negative patients were 39.1% (18/46) and 37.5% (6/16), respectively (x2 = 0.013, P = 0.908). Compared with the detection rates of HCVcAg in patients only infected with HCV, the detection rate of HCVcAg in HBeAg or HBV DNA negative patients infected with HCV and HBV were 60% (12/20) (x2 = 1.266, P = 0.261) and 37.5% (6/16) (x2 =7.635, P less than 0.01), respectively.

CONCLUSIONThe detection rate of HCVcAg in patients infected with HCV and HBV is relatively low. The reason is possibly that HBeAg inhibits duplication of HCV and decreases the expression of HCVcAg.

Coinfection ; immunology ; virology ; DNA, Viral ; Hepacivirus ; immunology ; Hepatitis B ; immunology ; virology ; Hepatitis B virus ; Hepatitis C Antigens ; blood ; Hepatitis C, Chronic ; immunology ; virology ; Humans

Animals ; Antigens, CD ; immunology ; Cytokines ; metabolism ; Hepacivirus ; immunology ; Hepatitis C ; immunology ; prevention & control ; virology ; Hepatitis C Antibodies ; biosynthesis ; immunology ; Hepatitis C Antigens ; immunology ; Humans ; Killer Cells, Natural ; immunology ; T-Lymphocytes ; immunology ; metabolism ; T-Lymphocytes, Regulatory ; immunology ; metabolism ; Viral Proteins ; immunology

Animals ; Hepacivirus ; genetics ; Hepatitis C ; immunology ; prevention & control ; therapy ; virology ; Humans ; Mutation ; Viral Hepatitis Vaccines ; immunology