MOLECULAR ANALYSIS OF POLIOVIRUS NEUTRALIZING EPITOPES

拟议研究的目的是有助于更详细地 对脊髓灰质炎病毒粒子的宿主抗体反应的分子描述。 分子生物学和免疫学相结合 A）脊髓灰质炎病毒上的免疫原性位点 1型病毒粒子，特别是中和决定簇，B）病毒 抗病毒抗体应答识别的抗原决定簇 易感和非易感宿主。 为了实现这些目标，单克隆 预定线性抗原特异性的抗体和单克隆抗体 识别病毒体决定簇的抗体将与 表达不同表位的重组DNA表达文库 病毒： 1)为了鉴定存在于病毒体表面的抗原决定簇， 中和抗体结合，导致感染性丧失; 分离抗原决定簇中的突变，其导致 表位识别的抗体和中和的产生 耐药病毒和 2)为了表征脊髓灰质炎病毒表位识别谱， 脊髓灰质炎病毒免疫小鼠和大鼠血清中发现的抗体， 来自脊髓灰质炎患者。 宿主对病毒体的免疫应答对于感染者来说是特别重要的。 深入了解脊髓灰质炎病毒疾病的发病机制。 健康 这项建议的相关性来自其对《公约》的贡献。 了解病毒致病的分子机制， 脊髓灰质炎病毒疫苗对宿主的保护作用。

The aim of the proposed research is to contribute to a more detailed molecular description of the host antibody response to poliovirus virions. It is proposed that a combination of molecular biologic and immunologic approaches be used to determine A) the immunogenic sites on the poliovirus type 1 virion, specifically the neutralization determinants, B) the viral antigenic determinants recognized by the antivirion antibody response of susceptible and nonsusceptible hosts. To achieve these goals, monoclonal antibodies of predetermined linear antigenic specificity and monoclonal antibodies recognizing virion determinants will be used in conjunction with a recombinant DNA expression library expressing the different epitopes of the virus: 1) To identify the antigenic determinants present on the virion surface to which neutralizing antibodies bind, resulting in loss of infectivity; to isolate mutations in the antigenic determinants which result in loss of epitope recognition by the antibodies and in generation of neutralization resistant viruses and 2) To characterize the spectrum of poliovirus epitopes recognized by antibodies found in the sera from poliovirus-immunized mice and rats and from poliomyelitis patients. The host immune response to the virion is particularly important for a thorough understanding of poliovirus disease pathogenesis. The health relatedness of this proposal derives from its contribution to the understanding of molecular mechanism of viral pathogenesis and to the basis of host protection by poliovirus vaccines.