MOLECULAR ANALYSIS OF POLIOVIRUS NEUTRALIZING EPITOPES

拟议研究的目的是为更详细的 宿主抗体对脊髓灰质炎病毒粒子反应的分子描述。 有人认为，分子生物学和免疫学的结合 用于确定A)脊髓灰质炎病毒上的免疫原部位的方法 1型病毒粒子，特别是中和决定因素，B)病毒 抗病毒粒子抗体反应所识别的抗原决定簇 敏感和不敏感的宿主。为了实现这些目标，克隆抗体 预定线性抗原特异性和单克隆性抗体 识别病毒粒子决定簇的抗体将与 表达不同表位的重组DNA表达文库 病毒： 1)鉴定存在于病毒粒子表面的抗原决定簇 哪些中和抗体结合，导致丧失传染性； 分离抗原决定簇中导致缺失的突变 抗体对表位的识别及中和作用的产生 耐药病毒和 2)表征由以下机构识别的脊髓灰质炎病毒表位的谱 在脊髓灰质炎病毒免疫的小鼠和大鼠的血清中发现抗体和 来自小儿麻痹症患者。 宿主对病毒粒子的免疫反应对 深入了解脊髓灰质炎病毒病的发病机制。健康 这项建议的关联性源于它对 对病毒致病分子机制及其基础的认识 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.