IFITM3-containing exosome as a novel mediator for anti-viral response in dengue virus infection
IFITM3-containing exosome as a novel mediator for anti-viral response in dengue virus infection
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含有 IFITM3 的外泌体作为登革热病毒感染抗病毒反应的新型介质
DOI：
10.1111/cmi.12339
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发表时间：
2015
影响因子：
3.4
通讯作者：
Li Mengfeng
中科院分区：
文献类型：
--
作者：
Zhu Xun;He Zhenjian;Yuan Jie;Wen Weitao;Huang Xuan;Hu Yiwen;Lin Cuiji;Pan Jing;Li Ran;Deng Haijing;Liao Shaowei;Zhou Rui;Wu Jueheng;Li Jun;Li Mengfeng
干扰素诱导跨膜蛋白1、2和3（IFITM 1、IFITM 2和IFITM 3）最近被鉴定为有效的抗病毒效应物，其功能是抑制多种包膜病毒的进入并调节细胞嗜性，而不依赖于病毒受体表达。然而，IFITMs对病毒感染的抗病毒作用和机制仍不完全了解和表征。在这项工作中，我们集中我们的调查的功能的细胞外IFITM 3蛋白。在DENV-2感染的细胞模型中，我们发现IFITM 3有助于基线和干扰素诱导的DENV进入抑制。最重要的是，我们的研究首次证明了细胞外环境中存在含有IFITM的外泌体，并鉴定了细胞外泌体在细胞间递送IFITM 3的能力，从而将其抗病毒作用从感染细胞传递到未感染细胞。因此，我们的研究结果为IFITM 3作用的基本机制提供了新的见解，这可能导致未来使用IFITM 3作为治疗剂开发外泌体介导的抗病毒策略。可以想象，IFITMs的基础和诱导水平以及IFITMs的细胞内和细胞外水平的变化可能预测个体之间或跨物种的登革病毒感染的严重程度。
Interferon‐inducible transmembrane proteins 1, 2 and 3 (IFITM1, IFITM2 and IFITM3) have recently been identified as potent antiviral effectors that function to suppress the entry of a broad range of enveloped viruses and modulate cellular tropism independent of viral receptor expression. However, the antiviral effect and mechanisms of IFITMs in response to viral infections remain incompletely understood and characterized. In this work, we focused our investigation on the function of the extracellular IFITM3 protein. In cell models of DENV‐2 infection, we found that IFITM3 contributed to both the baseline and interferon‐induced inhibition of DENV entry. Most importantly, our study for the first time demonstrated the presence of IFITM‐containing exosome in the extracellular environment, and identified an ability of cellular exosome to intercellularly deliver IFITM3 and thus transmit its antiviral effect from infected to non‐infected cells. Thus, our findings provide new insights in the basic mechanisms underlying the actions of IFITM3, which might lead to future development of exosome‐mediated anti‐viral strategies using IFITM3 as a therapeutic agent. Conceivably, variations in the basal and inducible levels of IFITMs, as well as in intracellular and extracellular levels of IFITMs, might predict the severity of dengue virus infections among individuals or across species.