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.

有些病毒尽管存在于唾液、母乳或精液中，但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（EV）可以抑制寨卡病毒感染。然而，抗病毒谱和潜在机制仍不清楚。在这里，我们应用脂质组学和流式细胞术来证明这些 EV 暴露磷脂酰丝氨酸 (PS)。通过阻断寨卡病毒在凋亡拟态过程中靶向的 PS 受体，它们会干扰病毒的附着和进入。因此，体外应用的 EV 的生理浓度可有效抑制凋亡拟态登革热、西尼罗河、基孔肯雅热、埃博拉病毒和水泡性口炎病毒的感染，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病毒的疱疹病毒。进入受体。我们的研究结果确定了体液中富含 PS-EV 的 EV 在通过病毒凋亡拟态抵抗感染的先天防御中的作用，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，而不是直接在人与人之间传播接触。