Antibodies in human sera specific to hypervariable region 1 of hepatitis C virus can block viral attachment

Abstract

It has been postulated that antibodies specific to the hypervariable region 1 (HVR1) within the putative envelope protein E2 of hepatitis C virus (HCV) can neutralize virus. We studied such antibodies in sere of patients who were infected in a single-source outbreak by a contaminated anti-D immunoglobulin preparation (HCV-AD78). The nucleotide sequences of cDNAs encoding HVR1 of HCV-AD78 were determined. The four major variants (HVR1.A, B, C, and D) were expressed as fusion proteins in Escherichia coli. Sixty- seven percent of sere contained antibodies to HVR1. A. Sera unrelated to infection of the outbreak also recognized HVR1. A but to a lesser extent (15%), suggesting that not all HVR1-specific antibodies are absolutely isolate-specific. Antibodies directed against individual variants of HVR1 were found in sere obtained early postinfection (p.i.) (≤ 1 year) but also in sere obtained several years later. An in vitro binding assay of HCV to tissue culture cells was employed to further characterize these sara. Five of seven sere that were obtained early p.i. prevented binding of HCV to cells. Preincubation of such sere with HVR1-specific fusion proteins restored binding of HCV to cells in four of five sera. These findings suggest that the majority of neutralizing antibodies are directed against HVR1. © 1995 Academic Press, Inc.