Measles virus (MeV) is a highly contagious human pathogen that continues to be a worldwide health burden. One of the challenges for the study of MeV spread is the identification of model systems that accurately reflect how MeV behaves in humans. For our studies, we use unpassaged, well-differentiated primary cultures of airway epithelial cells from human donor lungs to examine MeV infection and spread. Here, we show that the main components of the MeV ribonucleoprotein complex (RNP), the nucleocapsid and phosphoprotein, colocalize with the apical and circumapical F-actin networks. To better understand how MeV infections spread across the airway epithelium, we generated a recombinant virus incorporating chimeric fluorescent proteins in its RNP complex. By live cell imaging, we observed rapid movement of RNPs along the circumapical F-actin rings of newly infected cells. This strikingly rapid mechanism of horizontal trafficking across epithelia is consistent with the opening of pores between columnar cells by the viral membrane fusion apparatus. Our work provides mechanistic insights into how MeV rapidly spreads through airway epithelial cells, contributing to its extremely contagious nature.IMPORTANCE The ability of viral particles to directly spread cell to cell within the airways without particle release is considered to be highly advantageous to many respiratory viruses. Our previous studies in well-differentiated, primary human airway epithelial cells suggest that measles virus (MeV) spreads cell to cell by eliciting the formation of intercellular membrane pores. Based on a newly generated ribonucleoprotein complex (RNP) "tracker" virus, we document by live-cell microscopy that MeV RNPs move along F-actin rings before entering a new cell. Thus, rather than diffusing through the cytoplasm of a newly infected columnar cell, RNPs take advantage of the cytoskeletal infrastructure to rapidly spread laterally across the human airway epithelium. This results in rapid horizontal spread through the epithelium that does not require particle release.

中文翻译：

---

麻疹病毒核糖核蛋白复合物沿着 F-肌动蛋白环快速扩散到分化良好的原代人气道上皮细胞中。


麻疹病毒（MeV）是一种高度传染性的人类病原体，仍然是全球健康负担。 MeV 传播研究的挑战之一是识别准确反映 MeV 在人类中行为方式的模型系统。在我们的研究中，我们使用来自人类供体肺部的未传代、分化良好的气道上皮细胞原代培养物来检查 MeV 感染和传播。在这里，我们表明 MeV 核糖核蛋白复合物 (RNP) 的主要成分、核衣壳和磷蛋白与顶端和环顶端 F-肌动蛋白网络共定位。为了更好地了解 MeV 感染如何通过气道上皮传播，我们生成了一种在其 RNP 复合物中掺入嵌合荧光蛋白的重组病毒。通过活细胞成像，我们观察到 RNP 沿着新感染细胞的周围 F 肌动蛋白环快速移动。这种跨上皮水平运输的惊人快速机制与病毒膜融合装置打开柱状细胞之间的孔是一致的。我们的工作提供了关于 MeV 如何通过气道上皮细胞快速传播的机制见解，从而导致其极具传染性。 重要性 病毒颗粒在气道内直接在细胞间传播而不释放颗粒的能力被认为对许多呼吸道病毒非常有利。我们之前对分化良好的原代人气道上皮细胞的研究表明，麻疹病毒（MeV）通过引起细胞间膜孔的形成而在细胞之间传播。基于新生成的核糖核蛋白复合物（RNP）“追踪”病毒，我们通过活细胞显微镜记录了MeV RNP在进入新细胞之前沿着F-肌动蛋白环移动。 因此，RNP 不是通过新感染的柱状细胞的细胞质扩散，而是利用细胞骨架基础设施在人类气道上皮上快速横向扩散。这导致不需要颗粒释放的快速水平扩散通过上皮。