The soluble serum protein Gas6 bridges virion envelope phosphatidylserine to the TAM receptor tyrosine kinase Axl to mediate viral entry.

The soluble serum protein Gas6 bridges virion envelope phosphatidylserine to the TAM receptor tyrosine kinase Axl to mediate viral entry.
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DOI:
10.1016/j.chom.2011.03.012
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发表时间:
2011-04-21
影响因子:
30.3
通讯作者:
Chen IS
Chen IS
中科院分区:
医学1区
文献类型:
--
作者:
Morizono K;Xie Y;Olafsen T;Lee B;Dasgupta A;Wu AM;Chen IS

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病毒进入细胞通常通过病毒编码的包膜蛋白与特定细胞表面受体的结合而启动。研究缺乏包膜结合的慢病毒假型的感染性,我们仍然观察到一些细胞类型的高感染性。在进一步的研究中,我们发现这种感染性是由胎牛血清中的可溶性牛蛋白S或其人类同源物Gas 6赋予的。Gas6增强多种病毒包膜蛋白假型的天然感染性。Gas6通过将病毒体包膜磷脂酰丝氨酸桥接至靶细胞上的TAM受体酪氨酸激酶Axl来介导病毒与靶细胞的结合。凋亡细胞的吞噬清除已知涉及Gas6的桥接。牛痘病毒的复制,这是以前报道的使用凋亡模拟进入细胞,也增强了Gas6。这些结果揭示了病毒进入的另一种分子机制,可以扩大宿主范围并增强包膜病毒的感染性。
Virus entry into cells is typically initiated by binding of virally encoded envelope proteins to specific cell surface receptors. Studying infectivity of lentivirus pseudotypes lacking envelope binding, we still observed high infectivity for some cell types. On further investigation, we discovered that this infectivity is conferred by the soluble bovine protein S in fetal calf serum, or Gas6, its human homologue. Gas6 enhances native infectivity of pseudotypes of multiple viral envelope proteins. Gas6 mediates binding of the virus to target cells by bridging virion envelope phosphatidylserine to Axl, a TAM receptor tyrosine kinase on target cells. Phagocytic clearance of apoptotic cells is known to involve bridging by Gas6. Replication of vaccinia virus, which was previously reported to use apoptotic mimicry to enter cells, is also enhanced by Gas6. These results reveal an alternative molecular mechanism of viral entry that can broaden host range and enhance infectivity of enveloped viruses.
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