PARAMYXOVIRUS RECEPTOR RECOGNITION AND MEMBRANE FUSION

人类副粘病毒长期以来被认为是儿童和成人的重要呼吸道病原体。例如，人类副流感病毒3是肺炎和支气管炎的主要病因。副粘病毒进入细胞并通过膜融合在细胞间传播。随着我们对副粘病毒诱导融合机制的了解越来越多，它的融合蛋白在许多方面与流感病毒和人类免疫缺陷病毒的融合蛋白相似。然而，副粘病毒在促进融合的病毒中有一个非常重要的方面是独特的：它们的受体识别和促进融合的活性是由不同的刺突蛋白贡献的。这就需要一种机制，通过这种机制，两种蛋白质可以通过附着蛋白突介导的两种膜的并置，转化为融合蛋白突介导的融合。表征病毒与细胞受体相互作用的决定因素，以及这一事件如何改变两种副粘病毒刺突结构之间的关系以影响融合，是病毒感染过程和疾病进展机制的重要方面。这些目标的完成将有助于我们了解病毒与细胞表面早期相互作用的长期目标，这种相互作用是由病毒表面糖蛋白介导的。

The human paramyxoviruses have long been recognized as important respiratory pathogens of children, as well as adults. For example, human parainfluenza virus 3 is a major cause of pneumonia and bronchitis. Paramyxoviruses enter cells and spread between them via membrane fusion. As we learn more about the mechanism of paramyxovirus-induced fusion, it is becoming apparent that its fusion protein is similar in many aspects to those of the influenza and human immunodeficiency viruses. However, the paramyxoviruses are unique among fusion-promoting viruses in one very important aspect: their receptor recognition and fusion-promoting activities are contributed by different spike proteins. This necessitates a mechanism by which the two proteins can transduce the juxtaposition of the two membranes, mediated by the attachment protein spike, into their fusion, mediated by the fusion protein spike. Characterization of the determinants of the virus' interaction with cellular receptors and how this event alters the relationship between the two paramyxovirus spike structures to effect fusion are important aspects of the viral infectious process and the mechanism of disease progression. Completion of these aims will contribute to our long-term objective of understanding the early interactions of the virus and the cell surface, mediated by the viral surface glycoproteins.