ANALYSIS OF NEUTRALIZING EPITOPES ON ROTAVIRUS OUTER CAPSID PROTEINS

轮状病毒外衣壳蛋白中和表位分析

• 批准号: 3790874
• 负责人: Y HOSHINO
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3790874
• 关键词: Macaca mulatta; Rotavirus; antibody formation; capsid; chemical substitution; cross immunity; epitope mapping; genetic strain; monoclonal antibody; mutant; neutralizing antibody; nucleotides; protein sequence; serotyping; swine; virus antigen; virus protein

Two monoclonal antibodies which exhibited neutralizing activity against the outer capsid VP7 of two or more rotavirus serotypes were utilized to locate amino acid residues involved in the formation of cross-reactive epitopes. Neutralizing monoclonal antibody (N-mAb) raised against the VP7 or porcine rotavirus Gottfried strain (VP7 serotype 4) neutralizes not only VP7 serotype 4 strains but also VP7 serotype 3, 6, 9, or 10 viruses. N-mAb raised against the VP7 of rhesus monkey rotavirus MMU 18006 strain (VP7 serotype 3) neutralizes serotype 3 viruses as well as porcine serotype 4 viruses. Neutralization-resistant variants were selected in the presence of these monoclonal antibodies. Analysis of nucleotide and amino acid (aa) changes in antigenic variants of serotype 3, 4, 6, 9, or 10 rotavirus selected in the presence of the serotype cross-reactive N-mAbs showed that: (1) in addition to variable regions VR-5 (aa 87-100) and VR-7 (aa 141-150), variable regions VR-8 (aa 208-224) and VR-9 (aa 235-242) are involved in cross-reactive neutralization; (2) the site of amino acid substitution on mutant VP7 selected by a single N-mAb can vary, resulting in mutants which exhibit antigenic differences; (3) an amino acid substitution can occur at the same position on the VP7 of different serotypes selected by a single N-mAb; or (4) the location of an amino acid substitution on the mutant VP7 selected by a single N-mAb can vary depending on the rotavirus serotype.

具有中和活性的两种单抗 利用两种或两种以上轮状病毒血清型的外衣壳VP7进行定位 氨基酸残基参与交叉反应表位的形成。 抗VP7或猪VP7的中和单抗(N-mAb) 轮状病毒戈特弗里德株(VP7 4型)不仅能中和VP7 血清4型毒株以及VP7型3、6、9或10型病毒。N-单抗 针对恒河猴轮状病毒MMU 18006株(VP7)VP7的免疫原性研究 血清3)中和血清3病毒以及猪血清4 病毒。在存在的情况下，选择抗中和变异体 这些单抗中。 猪瘟病毒抗原变异体的核苷酸和氨基酸变化分析 血清3、4、6、9或10型轮状病毒 血清型交叉反应N-mAb显示：(1)除可变 VR-5区(AA 87-100)和VR-7区(AA 141-150)，可变区VR-8(AA 208-224)和VR-9(AA 235-242)参与交叉反应 中和；(2)突变体VP7上的氨基酸取代位点 由单个N-mAb选择的突变可以不同，导致突变体表现出 抗原性差异；(3)氨基酸替换可以在相同的 由单个N-mAb选择的不同血清型的VP7上的位置；或 (4)所选突变体VP7上氨基酸替换的位置 根据轮状病毒血清型的不同，单个N-mAb所产生的抗体也会有所不同。