The structure of an infectious immature flavivirus redefines viral architecture and maturation.

The structure of an infectious immature flavivirus redefines viral architecture and maturation.
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DOI:
10.1126/sciadv.abe4507
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发表时间:
2021-05
期刊:
影响因子:
13.6
通讯作者:
Watterson D
Watterson D
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Newton ND;Hardy JM;Modhiran N;Hugo LE;Amarilla AA;Bibby S;Venugopal H;Harrison JJ;Traves RJ;Hall RA;Hobson-Peters J;Coulibaly F;Watterson D

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传染性未成熟黄病毒的结构重新定义了病毒的结构和成熟。黄病毒是通过蚊子和蜱虫传播的严重人类疾病的原因。这些病毒使用强大的融合机制进入在病毒组装和流出过程中需要受到限制的靶细胞。分子伴侣前膜 (prM) 使病毒颗粒保持在不成熟、无法融合的状态,直到它们离开细胞。利用产生不成熟且具有传染性的颗粒的昆虫病毒,我们通过冷冻电子显微镜确定了第一个具有完整刺突的未成熟黄病毒的结构。出乎意料的是,prM 伴侣形成了一个支撑柱,将未成熟的刺突维持在不对称和直立状态,为酸化时的大规模重排做好了准备。沿着 prM 伴侣定义的路径,刺突的塌陷是必需的,并且多价免疫球蛋白 M 对其的抑制可阻止感染。修改后的架构和崩溃模型可能在黄病毒中保持不变。
The structure of an infectious immature flavivirus redefines viral architecture and maturation. Flaviviruses are the cause of severe human diseases transmitted by mosquitoes and ticks. These viruses use a potent fusion machinery to enter target cells that needs to be restrained during viral assembly and egress. A molecular chaperone, premembrane (prM) maintains the virus particles in an immature, fusion-incompetent state until they exit the cell. Taking advantage of an insect virus that produces particles that are both immature and infectious, we determined the structure of the first immature flavivirus with a complete spike by cryo–electron microscopy. Unexpectedly, the prM chaperone forms a supporting pillar that maintains the immature spike in an asymmetric and upright state, primed for large rearrangements upon acidification. The collapse of the spike along a path defined by the prM chaperone is required, and its inhibition by a multivalent immunoglobulin M blocks infection. The revised architecture and collapse model are likely to be conserved across flaviviruses.
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