人偏肺病毒感染发病机制及疫苗研究

Pathogenesis of human metapneumovirus infection and research on attenuated live vaccine

摘要:

人偏肺病毒（HMPV）在儿童呼吸道感染中的重要性越来越受到重视。HMPV感染往往在冬春季节流行，且1岁以内婴儿感染率最高，临床表现与呼吸道合胞病毒相似。机体通过病原识别受体（PRRs）识别HMPV病原相关模式分子（PAMP），其中Toll样受体3和4可能起重要作用，诱导I型干扰素及其它促炎症因子产生。采用定点诱变法成功制备F蛋白去N连接糖链减毒重组活疫苗株，在小鼠动物模型中证实该疫苗株有良好的免疫原性和免疫保护作用，具有临床应用前景。

Abstract:

Numerous studies have indicated that human metapneumovirus (hMPV) is an important viral pathogen in acute respiratory infections in children, presenting similar manifestations with respiratory syncytial virus (RSV). HMPV infection peaks in the winter-spring season and is more prevalent in younger ages, especially in children less than 1 year old. Host innate immune response has been implicated in recognition of pathogen-associated molecular patterns (PAMPs) of the virus. This recognition occurs through host pattern recognition receptors (PRRs). Toll like receptors (TLRs) are one of the largest class of PRRs which initiate and regulate adaptive immune responses. Some studies have indicated that TLR 3 and TLR 4 may play critical roles in hMPV infection. Construction of recombinant mutant viruses lacking one or two N-linked glycosylation sites in the F protein by using site-directed mutagenesis and reverse genetics may be helpful for developing attenuated live vaccines.