Have NEC Coat, Will Travel: Structural Basis of Membrane Budding During Nuclear Egress in Herpesviruses.

Have NEC Coat, Will Travel: Structural Basis of Membrane Budding During Nuclear Egress in Herpesviruses.
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DOI:
10.1016/bs.aivir.2016.07.002
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发表时间:
2017
影响因子:
--
通讯作者:
Heldwein EE
Heldwein EE
中科院分区:
医学2区
文献类型:
--
作者:
Bigalke JM;Heldwein EE

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疱疹病毒在有包膜病毒中是不寻常的,因为它们出芽两次,但获得一个包膜。此外,与在细胞核中复制的其他DNA病毒不同,疱疹病毒不通过穿过核孔或破坏核膜而离开细胞核。相反,疱疹病毒具有复杂的核逃逸机制,其中新生衣壳在内核膜处出芽以形成核周病毒体,其随后与外核膜融合,将衣壳释放到胞质溶胶中。这使它们成为极少数已知的能在核膜中出芽的病毒。在核出芽过程中获得的包膜不会最终进入成熟的病毒颗粒,而是允许衣壳从核转位到胞质溶胶中。病毒核出口复合物(NEC)是核出口的关键参与者,但其功能和机制仍然是个谜。最近的研究表明,NEC芽膜没有其他蛋白的帮助下,通过形成一个蜂窝状的外套,这建立了NEC作为第一个病毒编码的芽机器,在核,而不是细胞质,膜。这篇综述讨论了我们目前对NEC出芽机制的理解,重点是阐明NEC外壳的结构及其在疱疹病毒核逃逸过程中衣壳出芽中的作用的研究。
Herpesviruses are unusual among enveloped viruses because they bud twice yet acquire a single envelope. Furthermore, unlike other DNA viruses that replicate in the nucleus, herpesviruses do not exit it by passing through the nuclear pores or by rupturing the nuclear envelope. Instead, herpesviruses have a complex mechanism of nuclear escape whereby nascent capsids bud at the inner nuclear membrane to form perinuclear virions that subsequently fuse with the outer nuclear membrane, releasing capsids into the cytosol. This makes them some of the very few known viruses that bud into the nuclear envelope. The envelope acquired during nuclear budding does not end up in the mature viral particle but instead allows the capsid to translocate from the nucleus into the cytosol. The viral nuclear egress complex (NEC) is a critical player in the nuclear egress, yet its function and mechanism have remained enigmatic. Recent studies have demonstrated that the NEC buds membranes without the help of other proteins by forming a honeycomb coat, which established the NEC as the first virally encoded budding machine that operates at the nuclear, as opposed to cytoplasmic, membrane. This review discusses our current understanding of the NEC budding mechanism, with the emphasis on studies that illuminated the structure of the NEC coat and its role in capsid budding during herpesvirus nuclear escape.