Ray R, Khanna A, Lagging L M, Meyer K, Choo Q L, Ralston R, Houghton M, Becherer P R
Division of Infectious Diseases and Immunology, St. Louis University Health Sciences Center, Missouri 63110.
J Virol. 1994 Jul;68(7):4420-6. doi: 10.1128/JVI.68.7.4420-4426.1994.
Hepatitis C virus (HCV) accounts for most cases of acute and chronic non-A and non-B hepatitis with serious consequences that may lead to hepatocellular carcinoma. The putative envelope glycoproteins (E1 and E2) of HCV probably play a role in the pathophysiology of the virus. In order to map the immunodominant domains of the E1 glycoprotein, two epitopes from amino acid residues 210 to 223 (P1) and 315 to 327 (P2) were predicted from the HCV sequence. Immunization of mice with the synthetic peptides conjugated to bovine serum albumin induced an antibody response, and the antisera immunoprecipitated the E1 glycoprotein (approximately 33 kDa) of HCV expressed by recombinant vaccinia virus. A panel of HCV-infected human sera was also tested with the synthetic peptides by enzyme-linked immunosorbent assay for epitope-specific responses. Of 38 infected serum samples, 35 (92.1%) demonstrated a spectrum of reactivity to the P2 peptide. On the other hand, only 17 of 38 (44.7%) serum samples were reactive to the P1 peptide. Strains of HCV exhibit a striking genomic diversity. The predicted P1 epitope showed localization in the sequence-variable region, and the P2 epitope localized in a highly conserved domain. Results from this study suggest that the E1 glycoprotein of HCV contains at least two potential antigenic epitopes. Synthetic peptides corresponding to these epitopes and antisera to these peptides may serve as the monospecific immunological reagents to further determine the role of E1 glycoprotein in HCV infection.
丙型肝炎病毒（HCV）是急性和慢性非甲非乙型肝炎的主要病因，可导致严重后果，甚至引发肝细胞癌。HCV假定的包膜糖蛋白（E1和E2）可能在该病毒的病理生理过程中发挥作用。为了绘制E1糖蛋白的免疫显性区域，根据HCV序列预测了两个表位，分别位于氨基酸残基210至223（P1）和315至327（P2）处。用与牛血清白蛋白偶联的合成肽免疫小鼠可诱导抗体反应，抗血清能免疫沉淀重组痘苗病毒表达的HCV的E1糖蛋白（约33 kDa）。还用合成肽通过酶联免疫吸附测定法检测了一组HCV感染的人血清，以检测表位特异性反应。在38份感染血清样本中，35份（92.1%）对P2肽呈现出一系列反应性。另一方面，38份血清样本中只有17份（44.7%）对P1肽有反应。HCV毒株表现出显著的基因组多样性。预测的P1表位位于序列可变区，P2表位位于高度保守区域。本研究结果表明，HCV的E1糖蛋白至少包含两个潜在的抗原表位。与这些表位对应的合成肽以及针对这些肽的抗血清可作为单特异性免疫试剂，以进一步确定E1糖蛋白在HCV感染中的作用。
