Neural stem cell-derived exosomes mediate viral entry.
Neural stem cell-derived exosomes mediate viral entry.
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DOI：
10.2147/ijn.s70999
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发表时间：
2014
影响因子：
8
通讯作者：
Matthews QL
中科院分区：
文献类型：
--
作者：
Sims B;Gu L;Krendelchtchikov A;Matthews QL
病毒通过病毒配体与细胞受体的相互作用进入宿主细胞。病毒也可以以不依赖于受体的方式进入细胞。有关非受体依赖的病毒进入细胞的机制尚未完全阐明。细胞间的胞外体运输可能提供了一种病毒进入细胞的机制。为了研究外切体在细胞病毒进入中的作用，我们使用神经干细胞来源的外切体和腺病毒5型(Ad5)进行了原理验证研究。在柯萨奇病毒和腺病毒受体(CAR)缺陷的细胞中，Exosome显著促进Ad5的进入，其中Ad5的进入非常有限。外切体含有与磷脂酰丝氨酸结合的T细胞免疫球蛋白粘蛋白4(TIM-4)。经抗TIM-4抗体处理后，可显著阻断外切体介导的Ad5进入。神经干细胞来源的外切体以不依赖受体的方式介导Ad5的显著细胞进入。这种调节作用可能会被一种针对外切体TIM-4的抗体所阻碍。这组结果将有助于进一步阐明病毒/外切体途径，这将有助于通过开发治疗剂或疫苗来减少自然病毒感染。
Viruses enter host cells through interactions of viral ligands with cellular receptors. Viruses can also enter cells in a receptor-independent fashion. Mechanisms regarding the receptor-independent viral entry into cells have not been fully elucidated. Exosomal trafficking between cells may offer a mechanism by which viruses can enter cells. To investigate the role of exosomes on cellular viral entry, we employed neural stem cell-derived exosomes and adenovirus type 5 (Ad5) for the proof-of-principle study. Exosomes significantly enhanced Ad5 entry in Coxsackie virus and adenovirus receptor (CAR)-deficient cells, in which Ad5 only had very limited entry. The exosomes were shown to contain T-cell immunoglobulin mucin protein 4 (TIM-4), which binds phosphatidylserine. Treatment with anti-TIM-4 antibody significantly blocked the exosome-mediated Ad5 entry. Neural stem cell-derived exosomes mediated significant cellular entry of Ad5 in a receptor-independent fashion. This mediation may be hampered by an antibody specifically targeting TIM-4 on exosomes. This set of results will benefit further elucidation of virus/exosome pathways, which would contribute to reducing natural viral infection by developing therapeutic agents or vaccines.