Institute of Molecular Virology, Ulm University Medical Center, Ulm, Germany.
Institute of Virology, Philipps University Marburg, Marburg, Germany.
Nat Microbiol. 2024 Apr;9(4):905-921. doi: 10.1038/s41564-024-01637-6. Epub 2024 Mar 25.
Some viruses are rarely transmitted orally or sexually despite their presence in saliva, breast milk, or semen. We previously identified that extracellular vesicles (EVs) in semen and saliva inhibit Zika virus infection. However, the antiviral spectrum and underlying mechanism remained unclear. Here we applied lipidomics and flow cytometry to show that these EVs expose phosphatidylserine (PS). By blocking PS receptors, targeted by Zika virus in the process of apoptotic mimicry, they interfere with viral attachment and entry. Consequently, physiological concentrations of EVs applied in vitro efficiently inhibited infection by apoptotic mimicry dengue, West Nile, Chikungunya, Ebola and vesicular stomatitis viruses, but not severe acute respiratory syndrome coronavirus 2, human immunodeficiency virus 1, hepatitis C virus and herpesviruses that use other entry receptors. Our results identify the role of PS-rich EVs in body fluids in innate defence against infection via viral apoptotic mimicries, explaining why these viruses are primarily transmitted via PS-EV-deficient blood or blood-ingesting arthropods rather than direct human-to-human contact.
尽管某些病毒存在于唾液、母乳或精液中，但它们很少通过口腔或性传播。我们之前发现，精液和唾液中的细胞外囊泡（EVs）可抑制寨卡病毒感染。然而，其抗病毒谱和潜在机制仍不清楚。在此，我们应用脂质组学和流式细胞术表明，这些 EV 暴露了磷脂酰丝氨酸（PS）。通过阻断 PS 受体（寨卡病毒在细胞凋亡模拟过程中靶向的受体），它们干扰了病毒的附着和进入。因此，体外应用生理浓度的 EV 可有效抑制凋亡模拟的登革热、西尼罗河热、基孔肯雅热、埃博拉病毒和水疱性口炎病毒的感染，但不能抑制严重急性呼吸综合征冠状病毒 2、人类免疫缺陷病毒 1、丙型肝炎病毒和使用其他进入受体的疱疹病毒的感染。我们的研究结果表明，富含 PS 的 EV 在体液中通过病毒的凋亡模拟在先天防御感染中发挥作用，这解释了为什么这些病毒主要通过缺乏 PS-EV 的血液或吸血节肢动物传播，而不是通过直接的人与人接触传播。
