菲那病毒托斯卡纳病毒非典型地利用液泡酸性进入宿主细胞。

IF 6.7 1区 医学 Q1 Immunology and Microbiology PLoS Pathogens Pub Date : 2023-08-14 eCollection Date: 2023-08-01 DOI:10.1371/journal.ppat.1011562
Jana Koch, Qilin Xin, Martin Obr, Alicia Schäfer, Nina Rolfs, Holda A Anagho, Aiste Kudulyte, Lea Woltereck, Susann Kummer, Joaquin Campos, Zina M Uckeley, Lesley Bell-Sakyi, Hans-Georg Kräusslich, Florian Km Schur, Claudio Acuna, Pierre-Yves Lozach
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引用次数: 0

摘要

托斯卡纳病毒是地中海盆地夏季人类虫媒病毒病的主要原因。然而,早期病毒与宿主细胞的相互作用和进入机制仍然缺乏特征。通过研究iPSC衍生的人类神经元和细胞系,我们发现病毒与细胞表面的结合是特异性的,50%的结合病毒粒子在10分钟内被内吞。病毒离子进入Rab5a+早期内体,随后进入Rab7a+和LAMP-1+晚期内体区室。穿透需要完整的晚期内体,并在内化后30分钟内发生。病毒进入依赖于液泡酸化,病毒膜融合的最佳pH为5.5。在早期内体中,随着病毒粒子预暴露于微酸性pH的时间延长,pH阈值增加到5.8。引人注目的是,这些颗粒在进入pH低于融合阈值的晚期内体后仍然具有传染性。总的来说,我们的研究确定托斯卡纳病毒是一种晚期穿透病毒,并揭示了该病毒非典型地利用液泡酸性进入宿主细胞。
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The phenuivirus Toscana virus makes an atypical use of vacuolar acidity to enter host cells.

Toscana virus is a major cause of arboviral disease in humans in the Mediterranean basin during summer. However, early virus-host cell interactions and entry mechanisms remain poorly characterized. Investigating iPSC-derived human neurons and cell lines, we found that virus binding to the cell surface was specific, and 50% of bound virions were endocytosed within 10 min. Virions entered Rab5a+ early endosomes and, subsequently, Rab7a+ and LAMP-1+ late endosomal compartments. Penetration required intact late endosomes and occurred within 30 min following internalization. Virus entry relied on vacuolar acidification, with an optimal pH for viral membrane fusion at pH 5.5. The pH threshold increased to 5.8 with longer pre-exposure of virions to the slightly acidic pH in early endosomes. Strikingly, the particles remained infectious after entering late endosomes with a pH below the fusion threshold. Overall, our study establishes Toscana virus as a late-penetrating virus and reveals an atypical use of vacuolar acidity by this virus to enter host cells.

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来源期刊
PLoS Pathogens
PLoS Pathogens 生物-病毒学
CiteScore
11.40
自引率
3.00%
发文量
598
审稿时长
2 months
期刊介绍: Bacteria, fungi, parasites, prions and viruses cause a plethora of diseases that have important medical, agricultural, and economic consequences. Moreover, the study of microbes continues to provide novel insights into such fundamental processes as the molecular basis of cellular and organismal function.
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