Université Paris Cité, CNRS, Inserm, Institut Cochin, Paris, 75014, France.
Southampton Solent University, East Park Terrace, Southampton, SO14 0YN, UK.
EMBO Rep. 2024 Mar;25(3):1156-1175. doi: 10.1038/s44319-024-00069-x. Epub 2024 Feb 8.
Human rhinovirus is the most frequently isolated virus during severe exacerbations of chronic respiratory diseases, like chronic obstructive pulmonary disease. In this disease, alveolar macrophages display significantly diminished phagocytic functions that could be associated with bacterial superinfections. However, how human rhinovirus affects the functions of macrophages is largely unknown. Macrophages treated with HRV16 demonstrate deficient bacteria-killing activity, impaired phagolysosome biogenesis, and altered intracellular compartments. Using RNA sequencing, we identify the small GTPase ARL5b to be upregulated by the virus in primary human macrophages. Importantly, depletion of ARL5b rescues bacterial clearance and localization of endosomal markers in macrophages upon HRV16 exposure. In permissive cells, depletion of ARL5b increases the secretion of HRV16 virions. Thus, we identify ARL5b as a novel regulator of intracellular trafficking dynamics and phagolysosomal biogenesis in macrophages and as a restriction factor of HRV16 in permissive cells.
人鼻病毒是慢性呼吸道疾病（如慢性阻塞性肺疾病）严重恶化期间最常分离出的病毒。在这种疾病中，肺泡巨噬细胞的吞噬功能显著减弱，这可能与细菌的继发感染有关。然而，人鼻病毒如何影响巨噬细胞的功能在很大程度上仍是未知的。用 HRV16 处理的巨噬细胞显示出杀菌活性缺陷、吞噬溶酶体发生受损以及细胞内隔室改变。通过 RNA 测序，我们发现小 GTPase ARL5b 在原代人巨噬细胞中被病毒上调。重要的是，在 HRV16 暴露时，ARL5b 的耗竭可挽救细菌清除和内体标记物的定位。在允许的细胞中，ARL5b 的耗竭增加了 HRV16 病毒粒子的分泌。因此，我们确定 ARL5b 是巨噬细胞中细胞内运输动态和吞噬溶酶体发生的新型调节剂，并且是允许细胞中 HRV16 的限制因子。
