Quantitative analysis of antibody to hepatitis C virus envelope 2 glycoprotein in patients with chronic hepatitis C virus infection

Abstract

The significance of circulating antibody to hepatitis C HCV E1 corresponds to the pestiviral gp33/gp25 envevirus (HCV) envelope glycoprotein 2 (E2)/nonstructural lope glycoprotein and the flaviviral envelope protein protein 1 (NS1) glycoprotein was studied in 83 patients (M/E), whereas E2/NS1 corresponds to the pestiviral with chronic HCV infection diagnosed by polymerase gp53/gp55 envelope glycoprotein and the flaviviral chain reaction (PCR). E2/NS1 antibody was quantita-NS1. 1 Based on the greater homology between HCV tively examined by a passive hemagglutination test us-and the pestiviruses 1,4-6 and the absence of HCV E2/ ing recombinant E2/NS1 glycoprotein encompassing NS1 secretion into the medium by transfected mammaamino acids 388 to 664 of the HCV-H strain. The results lian Chinese hamster ovary cells, it has been proposed were correlated with clinical and virological features such as genotypes and viremic levels assessed by a com-that E2/NS1 more likely represents a virion envelope petitive reverse-transcription PCR assay. E2/NS1 anti-glycoprotein than the secreted NS1 of the flaviviruses. body was found in 73 patients (88%), and its occurrence Both the pestiviral gp53/gp55 and flaviviral NS1 glycowas related to viremic levels. E2/NS1 antibody titers proteins are known to elicit protective antibodies in were low in asymptomatic HCV carriers with low levels hosts. 7,8 HCV envelope glycoproteins can be considered of viral replication; 9 of 17 such patients tested positive possible candidates for vaccination against HCV infecfor E2/NS1 antibody (53%), compared with 64 of 66 tion. 9 However, the implications of the E2/NS1 antichronic hepatitis C patients (97%) (P õ .01). A significant direct relationship was observed between viremic levels body response in chronic HCV infection are not fully and E2/NS1 antibody titers (r Å .52, P õ .01). Of the 13 understood.patients with low viremic levels of õ10 6 copies/mL, only

Hepatitis C virus-related proteins in kidney tissue from hepatitis C virus-infected patients with cryoglobulinemic membranoproliferative glomerulonephritis

“…38 to the putative epitopes are detected in the cryoprecipitate and in the kidney biopsies of the same patients, confirming The role of cryoproteins in the pathogenesis of glomerulonephritis is suggested by the finding of IgM, IgG, and C3 that these antibodies have little or no neutralizing potential. 33 The same picture was found for nucleocapsid antigen, fraction at the sites of glomerular damage with the same distribution as the viral proteins. It can be argued that intrain that all patients displaying c22-3 Ag in the tissue had antic22-3 antibodies in the cryoprecipitates.…”

Conformational Epitopes Detected by Cross‐Reactive Antibodies to Envelope 2 Glycoprotein of the Hepatitis C Virus

“…A specific cell-binding assay developed by Rosa et al [6] showed that the ability to neutralize binding of E2 glycoprotein derived from the HCV-1a strain is distributed equally among sera from persons infected by HCV genotypes 1, 2, and 3. These observations raise a possibility that such a cross-reactive anti-E2 antibody, which is prevalent among infected persons, could be protective against HCV infection.While some reports [2][3][4][5] have shown a high prevalence of anti-E2 antibodies in HCV-infected persons, a few surveys [7,8] found a much lower prevalence. This divergence of results is thought to arise from a difference in the conformation of the E2 protein utilized in the antibody detection system; some researchers [3-5] used glycosylated undenatured E2 protein, but others [7, 8] used nonglycosylated or denatured protein.…”

“…While some reports [2][3][4][5] have shown a high prevalence of anti-E2 antibodies in HCV-infected persons, a few surveys [7,8] found a much lower prevalence. This divergence of results is thought to arise from a difference in the conformation of the E2 protein utilized in the antibody detection system; some researchers [3][4][5] used glycosylated undenatured E2 protein, but others [7,8] used nonglycosylated or denatured protein.…”

“…In this model, a correlation was established between titers of induced anti-E2 antibodies and protection. These findings suggest that anti-E2 antibody would be important for a successful hepatitis C vaccine.Previous studies [2][3][4][5] have shown that the prevalence of anti-E2 antibody among chronically HCV-infected patients is as high as that of core antibody regardless of viral genotype, even though the E2 sequence shows far less homology among genotypes than the core sequence. A specific cell-binding assay developed by Rosa et al [6] showed that the ability to neutralize binding of E2 glycoprotein derived from the HCV-1a strain is distributed equally among sera from persons infected by HCV genotypes 1, 2, and 3.…”

“…In the present study, we focused on this conformational antibody. Of two methodologically similar reports [3,4] concerning antibody responses of patient sera using E2 glycoprotein encompassing amino acids (aa) 388-664 of the HCV-H strain [9] (genotype 1a), one study [3] noted a prevalence of cross-reactive antibodies as high as 69% in HCV1b-infected patients. Based on this observation, we used an immunofluorescence technique to measure the antibody response of HCV-1b-infected patient sera against modified forms of E2 proteins derived from the HCV-H strain.…”