Virus entry. Lassa virus entry requires a trigger-induced receptor switch.

Virus entry. Lassa virus entry requires a trigger-induced receptor switch.
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DOI:
10.1126/science.1252480
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发表时间:
2014-06-27
期刊:
Science (New York, N.Y.)
影响因子:
--
通讯作者:
Brummelkamp TR
Brummelkamp TR
中科院分区:
其他
文献类型:
--
作者:
Jae LT;Raaben M;Herbert AS;Kuehne AI;Wirchnianski AS;Soh TK;Stubbs SH;Janssen H;Damme M;Saftig P;Whelan SP;Dye JM;Brummelkamp TR

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拉萨病毒从啮齿动物传播到人类,并可能导致致命的出血热。尽管鸡细胞具有广泛的嗜性,但据报道,30年前鸡细胞就能抵抗感染。我们发现,拉萨病毒很容易在禽类细胞中接触到其细胞表面受体α-dystroglan,但病毒在敏感物种中的进入涉及到一种依赖于pH的细胞内受体,即溶酶体驻留蛋白LAMP1。迭代单倍体筛选表明,唾液酸基转移酶ST3GAL4是病毒糖蛋白与LAMP1相互作用所必需的。LAMP1中的一个糖基化残基对于与Lassa病毒包膜蛋白的相互作用和随后的感染是必不可少的,该残基存在于敏感物种中,但在鸟类中不存在。LAMP1缺陷小鼠对Lassa病毒的抵抗力突显了这种受体开关在体内的相关性。
Lassa virus spreads from rodents to humans and can lead to lethal hemorrhagic fever. Despite its broad tropism, chicken cells were reported to resist infection thirty years ago. We show that Lassa virus readily engaged its cell surface receptor α-dystroglycan in avian cells, but virus entry in susceptible species involved a pH-dependent switch to an intracellular receptor, the lysosome-resident protein LAMP1. Iterative haploid screens revealed that the sialyltransferase ST3GAL4 was required for the interaction of the virus glycoprotein with LAMP1. A single glycosylated residue in LAMP1, present in susceptible species but absent in birds, was essential for interaction with the Lassa virus envelope protein and subsequent infection. The resistance of Lamp1-deficient mice to Lassa virus highlights the relevance of this receptor switch in vivo.
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期刊: Science (New York, N.Y.)
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Jae LT;Raaben M;Riemersma M;van Beusekom E;Blomen VA;Velds A;Kerkhoven RM;Carette JE;Topaloglu H;Meinecke P;Wessels MW;Lefeber DJ;Whelan SP;van Bokhoven H;Brummelkamp TR
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