Institute of Microbiology, University Hospital Center and University of Lausanne, Rue du Bugnon 48, CH-1011 Lausanne, Switzerland.
Institute of Microbiology, University Hospital Center and University of Lausanne, Rue du Bugnon 48, CH-1011 Lausanne, Switzerland; Spiez Laboratory, CH-3700 Spiez, Switzerland.
Virology. 2019 May;531:57-68. doi: 10.1016/j.virol.2019.02.013. Epub 2019 Feb 21.
Hantaviruses are emerging rodent-borne negative-strand RNA viruses associated with severe human diseases. Zoonotic transmission occurs via aerosols of contaminated rodent excreta and cells of the human respiratory epithelium represent likely early targets. Here we investigated cellular factors involved in entry of the pathogenic Old and New World hantaviruses Hantaan virus (HTNV) and Andes virus (ANDV) into human respiratory epithelial cells. Screening of a kinase inhibitor library using a biocontained recombinant vesicular stomatitis virus pseudotype platform revealed differential requirement for host kinases for HTNV and ANDV entry and provided first hints for an involvement of macropinocytosis. Examination of a selected panel of well-defined inhibitors of endocytosis confirmed that both HTNV and ANDV enter human respiratory epithelial cells via a pathway that critically depends on sodium proton exchangers and actin, hallmarks of macropinocytosis. However, HTNV and ANDV differed in their individual requirements for regulatory factors of macropinocytosis, indicating virus-specific differences.
汉坦病毒是新兴的啮齿动物传播的负链 RNA 病毒，与严重的人类疾病有关。通过受污染的啮齿动物排泄物的气溶胶发生人畜共患病传播，人类呼吸道上皮细胞可能是早期的主要目标。在这里，我们研究了参与致病性旧世界和新世界汉坦病毒汉滩病毒（HTNV）和安第斯病毒（ANDV）进入人类呼吸道上皮细胞的细胞因子。使用生物密封的重组水疱性口炎病毒假型平台筛选激酶抑制剂文库，发现 HTNV 和 ANDV 进入所需的宿主激酶存在差异，并首次提示巨胞饮作用的参与。对一组精选的明确的内吞作用抑制剂的检测证实，HTNV 和 ANDV 均通过严重依赖钠离子质子交换器和肌动蛋白的途径进入人类呼吸道上皮细胞，这是巨胞饮作用的标志。然而，HTNV 和 ANDV 在巨胞饮作用的调节因子的个体需求上存在差异，表明存在病毒特异性差异。
