MOLECULAR EPIDEMIOLOGY OF HUMAN PARAINFLUENZA VIRUS I

这项提议的长期目标是理解分子 人副流感病毒1型的结构和流行病学 因为它们与宿主免疫反应、疫苗开发、疾病 预测和预防。该病毒属于副粘病毒。 家庭，包括其他重要的人类病原体，如麻疹， 腮腺炎、呼吸道合胞病毒和副流感病毒3型。 HPIV-1是导致婴幼儿哮喘的最常见原因。 在世界各地每两年一次产生流行病。 拟议研究的具体目标是：1；确定基因 HPIV-1HN(血凝素-神经氨酸酶)的抗原多样性 25年收集的临床分离株；2.确定基因 与HPIV-1相关的单个种群的抗原多样性 流行性咽喉炎；3；测定儿童血清分布 针对先前定位的HPIV-1抗原位点的抗体 在一场咽喉病流行前后。 这项提案中的努力将针对以下方面 HPIV-1的HN分子的抗原性和遗传学。这个表面 糖蛋白可能在HPIV-1致病机制中起重要作用 在其他密切相关的病毒疾病中做类似的分子。它是 作为人类很大一部分保护性抗体反应的靶点， 可能含有重要的流行病学标志物。人物刻画 这种蛋白质的研究将涉及随着时间的推移检查病毒种群，从 不同的地理位置，在疫情期间。十四个反HN 将使用单克隆抗体来检测这些HPIV-1分离株和 将它们的HN蛋白与1957年型的抗原图进行比较 紧张。同样，这种类型毒株的RNA序列将用于 判断基因的变化。可能的HPIV-1毒株将被鉴定为 毒力上的任何差异。遗传和抗原性稳定 将寻找中和抗原部位，同时确认 他们在儿童中的免疫优势。总而言之，这些信息将 为分子流行病学和发病机制研究提供可靠依据 这应该会产生关于结构/功能关系的第一条线索 在HN基因、HN蛋白和中和性抗原位点之间， 走向现代疫苗战略的道路。 该提案将在以下4个领域中的3个领域提供重要信息 NIAID和WHO最近联合推荐的HPIV-1研究 研修班。

The long-term objectives of this proposal are to understand the molecular structure and epidemiology of human parainfluenza virus type one (HPIV-1) as they relate to the host immune response, vaccine development, disease prediction and prevention. This virus belongs to the paramyxovirus family, which includes other important human pathogens such as measles, mumps, respiratory syncytial virus, and parainfluenza virus type 3. HPIV-1 is the most common cause of croup in infants and young children generating epidemics throughout the world on a biennial basis. Specific aims of the proposed research are: 1; To determine the genetic and antigenic diversity in the HN (hemagglutinin-neuraminidase) of HPIV-1 clinical isolates collected over 25 years; 2; To determine the genetic and antigenic diversity in a single HPIV-1 population associated with epidemic croup; 3; To determine in children the distribution of serum antibody directed toward the previously mapped HPIV-1 antigenic sites before and after a croup epidemic. The effort in this proposal will be directed toward characterizing antigenically and genetically the HN molecule of HPIV-1. This surface glycoprotein probably plays an important role in HPIV-1 pathogenesis, as do similar molecules in other closely related viral diseases. It is the target for a large portion of the protective antibody response in humans, and could contain important epidemiologic markers. The characterization of this protein will involve examining viral populations over time, from different geographic locations, and during an epidemic. Fourteen anti-HN monoclonal antibodies will be used to examine these HPIV-1 isolates and to compare their HN proteins to the antigenic map of the 1957 type strain. Similarly, the RNA sequence of this type strain will be used to judge genetic changes. Possible strains of HPIV-1 will be identified as will any differences in virulence. Genetically and antigenically stable neutralizing antigenic sites will be sought along with confirmation of their immunodominance in children. Together, this information will provide a reliable foundation of molecular epidemiology and pathogenesis that should yield the first clues to structure/function relationships among the HN gene, HN protein and neutralizing antigenic sites, and point the way toward modern vaccine strategies. This proposal will provide important information in 3 of the 4 areas of research recently recommended for HPIV-1 by a combined NIAID and WHO workshop.