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 usand 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 antiglycoprotein 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 Γ΅ .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 Γ
.52, P Γ΅ .01). Of the 13 understood.
patients with low viremic levels of Γ΅10 6 copies/mL, only Previous reports showed that the E2/NS1 antibody 5 tested positive for E2/NS1 antibody (38%), whereas 68 response can occur in patients with chronic HCV infecof the 70 patients with viremic levels of Β’10 6 copies/mL tion. [10][11][12][13][14][15] The prevalence, however, differs considerably had it (97%) (P Γ΅ .01). As for the relation to HCV genoamong studies. This may be attributable to differences types, no difference was seen in E2/NS1 antibody titers in antigens and assay systems used. E2/NS1 antibody among genotypes examined (1b, 2a, and 2b). These findings suggest that the E2/NS1 antibody tested exhibits no may not be detected with synthetic peptides or recombineutralizing activity in chronic HCV infection but may nant polypeptides expressed in yeast or Escherichia serve as a serological indicator of active virus replicacoli that are nonglycosylated and differ from native E2/ tion. (HEPATOLOGY 1996;23:947-952.) NS1 glycoprotein. Moreover, the antigens are denatured in Western blot analysis. Hepatitis C virus (HCV) is distantly related to pesti-
The coexistence of E2/NS1 antibody and viremia inviruses and flaviviruses, 1 and putative HCV envelope glycoprotein 1 (E1) and envelope glycoprotein 2 (E2)/ dicates that this antibody is unlikely to have neutraliznonstructural protein 1 (NS1) have been identified. 2,3 ing activity in chronic HCV infection. However, no quantitative analysis has been performed to investigate the relation of the E2/NS1 antibody response to Abbreviations: HCV, hepatitis C virus; E1, envelope glycoprotein 1; E2, HCV replicative levels. Furthermore, it remains uncerenvelope glycoprotein 2; NS1, nonstructural protein 1; PCR, polymerase chain reaction.
tain whether E2/NS1 antibody response levels have
From the