Okuno Y, Isegawa Y, Sasao F, Ueda S
Department of Preventive Medicine, Osaka University, Japan.
J Virol. 1993 May;67(5):2552-8. doi: 10.1128/JVI.67.5.2552-2558.1993.
When mice were immunized with the A/Okuda/57 (H2N2) strain of influenza virus, a unique monoclonal antibody designated C179 was obtained. Although C179 was confirmed to recognize the hemagglutinin (HA) glycoprotein by immunoprecipitation assays, it did not show hemagglutination inhibition activity to any of the strains of the three subtypes of influenza A virus. However, it neutralized all of the H1 and H2 strains but not the H3 strains. Moreover, it inhibited polykaryon formation induced by the H1 and H2 strains but not by the H3 strains. Two antigenic variants against C179 were obtained, and nucleotide sequence analysis revealed that amino acid sequences, from 318 to 322 of HA1 and from 47 to 58 of HA2, conserved among H1 and H2 strains were responsible for the recognition of C179. Since the two sites were located close to each other at the middle of the stem region of the HA molecule, C179 seemed to recognize these sites conformationally. These data indicated that binding of C179 to the stem region of HA inhibits the fusion activity of HA and thus results in virus neutralization and inhibition of cell-cell fusion. This is the first report which describes the presence of conserved antigenic sites on HA not only in a specific subtype but also in two subtypes of influenza A virus.
当用A/Okuda/57（H2N2）流感病毒株免疫小鼠时，获得了一种独特的单克隆抗体，命名为C179。尽管通过免疫沉淀试验证实C179可识别血凝素（HA）糖蛋白，但它对甲型流感病毒三个亚型的任何毒株均未表现出血凝抑制活性。然而，它能中和所有H1和H2毒株，但不能中和H3毒株。此外，它能抑制由H1和H2毒株诱导的多核体形成，但不能抑制H3毒株诱导的多核体形成。获得了两种针对C179的抗原变异体，核苷酸序列分析表明，HA1的318至322位氨基酸序列以及HA2的47至58位氨基酸序列，在H1和H2毒株中保守，是C179识别的原因。由于这两个位点在HA分子茎区中部彼此靠近，C179似乎以构象方式识别这些位点。这些数据表明，C179与HA茎区的结合抑制了HA的融合活性，从而导致病毒中和以及细胞间融合的抑制。这是第一份描述HA上不仅在特定亚型而且在甲型流感病毒两个亚型中存在保守抗原位点的报告。
