MOLECULAR EPIDEMIOLOGY OF HUMAN PARAINFLUENZA VIRUS I

这项提案的长期目标是了解分子 人副流感病毒1型（HPIV-1）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。 这种病毒属于副粘病毒 家族，其中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是婴幼儿哮吼的最常见原因 每两年在世界范围内产生流行病。 本研究的具体目的是：1、确定遗传 HPIV-1的HN（血凝素-神经氨酸酶）和抗原多样性 收集25年以上的临床分离株; 2;确定遗传 和抗原多样性在一个单一的HPIV-1人口与 流行性喉炎; 3.确定儿童血清中 针对先前定位的HPIV-1抗原位点的抗体 在哮吼流行病前后 本提案中的努力将针对表征 抗原性和遗传学上的HPIV-1的HN分子。 该表面 糖蛋白可能在HPIV-1发病机制中起重要作用， 在其他密切相关的病毒性疾病中也有类似的分子。 是 靶向人体中大部分的保护性抗体应答， 并可能含有重要的流行病学标志物。 表征 这种蛋白质的研究将涉及随着时间的推移检查病毒种群， 不同的地理位置，以及在流行病期间。 14抗HN 将使用单克隆抗体检测这些HPIV-1分离株， 将他们的HN蛋白与1957年类型的抗原图谱进行比较 株 类似地，该模式菌株的RNA序列将用于 判断基因变化。 可能的HPIV-1菌株将被鉴定为 毒力的差异。 遗传和抗原稳定 将寻找中和抗原位点，沿着确认 儿童的免疫优势。 总之，这些信息将 为分子流行病学和发病机制提供可靠的基础 这将为结构/功能关系提供第一条线索， 在HN基因、HN蛋白和中和抗原位点之间， 现代疫苗策略的方向。 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联合最近推荐的HPIV-1研究 车间

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.