glycoprotein-e2--hepatitis-c-virus and Hepatitis--Viral--Human

L-ficolin, one of lectin families, is a recently identified complement factor that initiates lectin pathway of complement. Little is known about its role in viral hepatitis. In the present study, we found that L-ficolin in serum from 103 patients with hepatitis C virus (HCV), were significantly higher than that in 150 healthy controls. We further found that L-ficolin expressions were significantly increased in vitro study by HCV JFH-1 infected human hepatocyte cell line Huh7.5.1. Investigation of the mechanisms of the L-ficolin action on HCV demonstrated that L-ficolin protein could recognize and bind to envelope glycoproteins E1 and E2 of HCV, activating the lectin complement pathway-mediated cytolytic activity in HCV-infected hepatocyte. This interaction between L-ficolin and HCV E1 and E2 glycoproteins was attributed to the N-glycans of E1 and E2. These findings provide new insights into the biological functions of L-ficolin in clinically important hepatic viral diseases.

Topics: Cell Line; Complement Activation; Cytotoxicity, Immunologic; Female; Ficolins; Hepacivirus; Hepatitis, Viral, Human; Hepatocytes; Humans; Lectins; Male; Middle Aged; Polysaccharides; Protein Binding; Viral Envelope Proteins

Changes in the deduced amino acid sequence of the envelope 2 (E2) region of the GB virus C/hepatitis G virus (GBV-C/HGV) were analyzed to investigate whether or not the region contributes to persistent infection with the virus.. Eight patients with acute hepatitis C and 1 patient with acute hepatitis of unknown etiology were included in the study. GBV-C/HGV RNA was detected in 6 patients, including the patient with hepatitis of unknown origin. The nucleotide sequence of the E2 region of hepatitis C virus (HCV) and GBV-C/HGV was determined by direct sequencing of polymerase chain reaction products in 5 patients with HCV infection and in 6 patients with GBV-C/HGV infection twice during the period of early infection and several months or years later in each patient.. The mean substitution rate of the deduced amino acid sequence in the E2 region was over 100 times lower (p < 0.001) in GBV-C/HGV (0.01 +/- 0.04/month/100 sites) than in HCV (2.4 +/- 1.7/month/100 sites). The amino acid sequence of the loop domain of GBV-C/HGV-E2 did not change in any of the 6 patients. On the other hand, the sequence of the hypervariable region of HCV-E2 changed remarkably (5.9 +/- 4.3/month/100 sites). No amino acid substitution in the loop domain was observed in 7 additional patients who showed persistent GBV-C/HGV viremia for more than 2 years.. These results indicate that changes in the amino acid sequence of the E2 region are not involved in the mechanism of persistent GBV-C/HGV infection.

Topics: Acute Disease; Adult; Amino Acid Sequence; Amino Acid Substitution; Female; Flaviviridae; Hepacivirus; Hepatitis C; Hepatitis, Viral, Human; Humans; Male; Middle Aged; Molecular Sequence Data; Sequence Alignment; Sequence Analysis, Protein; Viral Envelope Proteins

GB virus C (GBV-C)/hepatitis G virus (HGV) is a recently recognized parenterally and sexually transmitted agent. The prevalence of GBV-C/HGV markers in Canadian blood donors has not been previously studied and was therefore determined.. Blood donors [identity unlinked (IU), short-term temporarily deferred (STTD) and autologous groups] and donor samples with antibodies to hepatitis C (anti-HCV) or hepatitis B core were tested for GBV-C/HGV RNA and for antibodies to E2 antigen (anti-E2).. GBV-C/HGV RNA was found in 1.1% and anti-E2 in 7.3% of the combined IU/STTD donor group. Viremia was much more common in anti-HCV-positive samples (12.5%); anti-E2 was present in >50% of this group. In the STTD group, female gender was significantly associated with viremia.. GBV-C/HGV infection is relatively common in Canadian donors, and a small proportion are viremic. The association of female gender and viremia was unexpected. Further study is needed to clarify the epidemiology and natural history of GBV-C/HGV infection.

Topics: Adolescent; Adult; Aged; Antibodies, Viral; Canada; Confidence Intervals; Female; Flaviviridae; Hepatitis B Core Antigens; Hepatitis C Antibodies; Hepatitis, Viral, Human; Humans; Male; Middle Aged; Prevalence; RNA, Viral; Seroepidemiologic Studies; Viral Envelope Proteins; Viremia

GB virus C/hepatitis G virus (GBV-C/HGV) is related distantly to hepatitis C virus (HCV). HCV has a hypervariable region (HVR), and exists as quasispecies in vivo. Although GBV-C/HGV also has replaceable amino acids in the presumed antigenic region, the existence and fluctuation of population of heterogeneous virus have not been evaluated. In this study, the heterogeneity of GBV-C/HGV and HCV was investigated by the single-strand conformation polymorphism (SSCP) analysis in six concomitantly infected patients. Two patients were observed for 4 years without any treatment, and four were treated with interferon-alpha (IFN). By SSCP analysis, amplicons of GBV-C/HGV RNA were separated into 1-5 bands on gels for each patient. The amplicons had different nucleotide but the same amino acid sequences in the presumed antigenic region. The amplicons of HCV RNA, separated into 1-4 bands, had different nucleotide and amino acid sequences in the HVR. In the two patients without treatment, the predominant strain of GBV-C/HGV was unchanged for the 4 years. In the four patients administered IFN, some strains of GBV-C/HGV disappeared after IFN therapy, whereas other strains persisted. The mean genetic distance among GBV-C/HGV strains represented by SSCP analysis was significantly lower than that of HCV (P < 0.05). The data indicate that: 1) GBV-C/HGV can be devoid of antigenic drift unlike HCV; 2) GBV-C/HGV has no HVR as seen in HCV in the presumed antigenic region; and 3) the sensitivity to IFN differs among GBV-C/HGV strains in the same hosts, as with HCV.

Topics: Adult; Aged; Amino Acid Sequence; Antiviral Agents; Base Sequence; DNA, Viral; Female; Flaviviridae; Genetic Heterogeneity; Hepacivirus; Hepatitis C; Hepatitis, Viral, Human; Humans; Interferon-alpha; Male; Middle Aged; Molecular Sequence Data; Polymorphism, Single-Stranded Conformational; Sequence Homology, Amino Acid; Sequence Homology, Nucleic Acid; Viral Envelope Proteins

The epidemiology and disease association for the GB virus type C (GBV-C) or hepatitis G virus (HGV) are poorly understood.. This study describes the exposure rates to GBV-C/HGV in diverse Australian population groups by testing for current infection and evidence of past infection with a reverse transcriptase polymerase chain reaction and an anti-E2 enzyme-linked immunosorbent assay, respectively. Subjects included volunteer blood donors, hepatitis C antibody (anti-HCV)-positive donors, children, hemodialysis patients, pregnant women attending a prenatal clinic, injecting drug users (IVDUs), and adult hemophiliacs.. Combined GBV-C RNA and E2 antibody prevalence was 6.5 percent (6/93) in children, 13.3 percent (75/565) in blood donors, 14 percent (14/99) in pregnant women, 22.5 percent (18/80) in hemodialysis patients, 80 percent (56/70) in anti-HCV-positive donors, 88.6 percent (31/35) in IVDUs, and 85.7 percent (54/63) in adult hemophiliacs. Children had the lowest antibody rate, 1.1 percent, whereas the rate was 10.8 percent for blood donors and rose to 45.7 percent for IVDUs, 57.1 percent for anti-HCV-positive donors, and 74.6 percent for hemophiliacs. In contrast, current infection rates were comparable for children, blood donors, and pregnant women (5.4, 2.6, and 6%, respectively), rising to 11.1 percent for hemophiliacs, 24.3 percent for anti-HCV-positive donors, and 48.6 percent for IVDUs. Ten of 12 blood donors had persistent viremia, while 2 had recent infections, 1 with apparent resolution.. Exposure to GBV-C can commence at an early age, although ongoing exposure may also occur among adults with no apparent risk factors. GBV-C RNA positivity was not associated with abnormal plasma alanine aminotransferase levels among blood donors.

Topics: Adult; Antibodies, Viral; Australia; Blood Donors; Child; Child, Preschool; Female; Flaviviridae; Hepatitis, Viral, Human; Humans; Infant; Male; Polymerase Chain Reaction; Pregnancy; RNA-Directed DNA Polymerase; RNA, Viral; Viral Envelope Proteins

An ELISA was developed for detection of antibodies to GB virus C (GBV-C) using a recombinant E2 protein expressed in CHO cells. Seroconversion to anti-E2 positivity was noted among several persons infected with GBV-C RNA-positive blood through transfusion. Of 6 blood recipients infected by GBV-C RNA-positive donors, 4 (67%) became anti-E2 positive and cleared their viremia. Thus, anti-E2 seroconversion is associated with viral clearance. The prevalence of antibodies to E2 was relatively low (3.0%-8.1%) in volunteer blood donors but was higher in several other groups, including plasmapheresis donors (34.0%), intravenous drug users (85.2%), and West African subjects (13.3%), all of whom tested negative by GBV-C reverse-transcription polymerase chain reaction (RT-PCR). These data demonstrate that testing for anti-E2 should greatly extend the ability of RT-PCR to define the epidemiology and clinical significance of GBV-C.

Topics: Africa; Animals; Antibodies, Viral; Blood Donors; CHO Cells; Cricetinae; Enzyme-Linked Immunosorbent Assay; Flaviviridae; Hepatitis, Viral, Human; Humans; Plasmapheresis; Polymerase Chain Reaction; Prevalence; Recombinant Proteins; RNA, Viral; Substance Abuse, Intravenous; Transfusion Reaction; Viral Envelope Proteins