Measles virus airway epithelium entry, and rapid cell-to-cell spread

麻疹病毒进入气道上皮并在细胞间快速传播

• 批准号: 9288122
• 负责人: ROBERTO B. CATTANEO
• 金额: $ 19.47万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-06-07 至 2018-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9288122
• 关键词: Address; Adherens Junction; Alveolar; Apical; B-Lymphocytes; Back; Binding Proteins; Caliber; Cell membrane; Cells; Cessation of life; Columnar Cell; Coughing; Cytoskeleton; Dendritic Cells; Discipline; Disease Outbreaks; Epithelial; Epithelial Cells; Epithelium; Glycoproteins; Green Fluorescent Proteins; Human; Immune; Infection; Knowledge; Link; Lung diseases; Lymphatic; Lymphocyte Activation; Measles; Measles virus; Membrane; Membrane Fusion; Myeloid Cells; Nature; Organ; Phase; Process; Proteins; Public Health; Receptor Signaling; Sneezing; Spleen; Structure; Structure of respiratory epithelium; Surface; Testing; Thymus Gland; Tight Junctions; Trachea; Travel; Vaccination; Viral; Virus; Virus Diseases; airway epithelium; base; blind; contagion; extracellular; lymph nodes; macrophage; monocyte; nectin; particle; pathogen; preference; receptor; respiratory virus; small molecule inhibitor

Measles virus (MeV) is the most contagious human respiratory virus, but within natural hosts MeV infections are largely cell-associated. We recently documented how virus-elicited intercellular pores facilitate rapid MeV spread in well-differentiated primary airway epithelia from human donors. Here we seek to characterize the mechanisms that promote airway epithelium entry and rapid cell-to-cell spread. Our central hypothesis is that MeV developed cell-based strategies for both processes. In aim 1 we will characterize which myeloid cells transfer infectivity to airway epithelia, and how. In aim 2 we will identify the cytoskeletal structures and processes co-opted by MeV to promote its rapid epithelial spread. Our studies will reveal how MeV spreads more rapidly than other viruses in human airway epithelia, which accounts for its exceptional contagion efficiency.

麻疹病毒 (MeV) 是传染性最强的人类呼吸道病毒，但在自然宿主内，MeV 感染主要与细胞相关。我们最近记录了病毒引起的细胞间孔如何促进 MeV 在人类供体分化良好的初级气道上皮细胞中快速传播。在这里，我们试图描述促进气道上皮进入和快速细胞间传播的机制。我们的中心假设是 MeV 为这两个过程开发了基于细胞的策略。在目标 1 中，我们将描述哪些骨髓细胞将感染性转移至气道上皮，以及如何转移感染性。在目标 2 中，我们将确定 MeV 所利用的细胞骨架结构和过程，以促进其快速上皮扩散。我们的研究将揭示 MeV 如何在人类呼吸道上皮细胞中比其他病毒传播得更快，这就是其卓越的传染效率的原因。

项目成果

Cell-to-Cell Contact and Nectin-4 Govern Spread of Measles Virus from Primary Human Myeloid Cells to Primary Human Airway Epithelial Cells.

细胞间接触和 Nectin-4 控制麻疹病毒从原代人骨髓细胞传播到原代人气道上皮细胞。

• DOI: 10.1128/jvi.00266-16
• 发表时间: 2016
• 期刊: Journal of virology
• 影响因子: 5.4
• 作者: Singh,BrajeshK;Li,Ni;Mark,AnnaC;Mateo,Mathieu;Cattaneo,Roberto;Sinn,PatrickL
• 通讯作者: Sinn,PatrickL