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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >In vitro modeling of respiratory syncytial virus infection of pediatric bronchial epithelium, the primary target of infection in vivo
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In vitro modeling of respiratory syncytial virus infection of pediatric bronchial epithelium, the primary target of infection in vivo

机译：小儿支气管上皮呼吸道合胞病毒感染的体外建模，这是体内感染的主要目标

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摘要

Respiratory syncytial virus (RSV) is the major viral cause of severe pulmonary disease in young infants worldwide. However, the mechanisms by which RSV causes disease in humans remain poorly understood. To help bridge this gap, we developed an ex vivo/ in vitro model of RSV infection based on well-differentiated primary pediatric bronchial epithelial cells (WD-PBECs), the primary targets of RSV infection in vivo. Our RSV/WD-PBEC model demonstrated remarkable similarities to hallmarks of RSV infection in infant lungs. These hallmarks included restriction of infection to noncontiguous or small clumps of apical ciliated and occasional nonciliated epithelial cells, apoptosis and sloughing of apical epithelial cells, occasional syncytium formation, goblet cell hyperpla-sia/metaplasia, and mucus hypersecretion. RSV was shed exclusively from the apical surface at titers consistent with those in airway aspirates from hospitalized infants. Furthermore, secretion of proinflammatory chemokines such as CXCL10, CCL5, IL-6, and CXCL8 reflected those chemokines present in airway aspirates. Interestingly, a recent RSV clinical isolate induced more cytopatho-genesis than the prototypic A2 strain. Our findings indicate that this RSV/WD-PBEC model provides an authentic surrogate for RSV infection of airway epithelium in vivo. As such, this model may provide insights into RSV pathogenesis in humans that ultimately lead to successful RSV vaccines or therapeutics.
机译：呼吸道合胞病毒（RSV）是全世界幼儿中严重肺部疾病的主要病毒原因。但是，RSV导致人类疾病的机制仍知之甚少。为了弥合这一差距，我们开发了基于高度分化的小儿支气管上皮细胞（WD-PBECs）的RSV感染的离体/体外模型，WD-PBECs是体内RSV感染的主要目标。我们的RSV / WD-PBEC模型显示出与婴儿肺中RSV感染特征的显着相似之处。这些标志包括将感染限制在不连续的或小块的顶端纤毛和偶发的非纤毛上皮细胞，顶端上皮细胞的凋亡和脱落，偶尔的合胞体形成，杯状细胞增生/间质增生和粘液分泌过多。 RSV完全从根尖表面脱落，滴度与住院婴儿呼吸道吸出液的滴度一致。此外，促炎性趋化因子如CXCL10，CCL5，IL-6和CXCL8的分泌反映出气道抽吸物中存在的那些趋化因子。有趣的是，最近的RSV临床分离株比原型A2株诱导更多的细胞病变。我们的发现表明，这种RSV / WD-PBEC模型为RSV体内感染气道上皮提供了可靠的替代品。这样，该模型可以提供对人类RSV发病机理的见解，从而最终导致成功的RSV疫苗或治疗方法的成功。

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    Remi Villenave; Surendran Thavagnanam; Severine Sarlang; Jeremy Parker; Isobel Douglas; Grzegorz Skibinski; Liam G. Heaney; James P. McKaigue; Peter V. Coyle; Michael D. Shields; Ultan F. Power;

  • 作者单位

    Centre for Infection and Immunity, School of Medicine, Dentistry and Biomedical Sciences, Queens University Belfast, Belfast BT9 7BL, Northern Ireland;

    Centre for Infection and Immunity, School of Medicine, Dentistry and Biomedical Sciences, Queens University Belfast, Belfast BT9 7BL, Northern Ireland,The Royal Belfast Hospital for Sick Children, Belfast BT12 6BE, Northern Ireland;

    Centre for Infection and Immunity, School of Medicine, Dentistry and Biomedical Sciences, Queens University Belfast, Belfast BT9 7BL, Northern Ireland;

    Centre for Infection and Immunity, School of Medicine, Dentistry and Biomedical Sciences, Queens University Belfast, Belfast BT9 7BL, Northern Ireland;

    The Royal Belfast Hospital for Sick Children, Belfast BT12 6BE, Northern Ireland;

    Centre for Infection and Immunity, School of Medicine, Dentistry and Biomedical Sciences, Queens University Belfast, Belfast BT9 7BL, Northern Ireland;

    Centre for Infection and Immunity, School of Medicine, Dentistry and Biomedical Sciences, Queens University Belfast, Belfast BT9 7BL, Northern Ireland;

    The Royal Belfast Hospital for Sick Children, Belfast BT12 6BE, Northern Ireland;

    The Regional Virus Laboratory, Belfast Trust, Belfast BT12 6BA, Northern Ireland;

    Centre for Infection and Immunity, School of Medicine, Dentistry and Biomedical Sciences, Queens University Belfast, Belfast BT9 7BL, Northern Ireland,The Royal Belfast Hospital for Sick Children, Belfast BT12 6BE, Northern Ireland;

    Centre for Infection and Immunity, School of Medicine, Dentistry and Biomedical Sciences, Queens University Belfast, Belfast BT9 7BL, Northern Ireland;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    primary airway epithelial cells; virus-host interaction; lung epithelium model;

    机译：气道上皮细胞病毒-宿​​主相互作用;肺上皮模型;

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