The curious case of arenavirus entry, and its inhibition.
The curious case of arenavirus entry, and its inhibition.
复制标题
DOI：
10.3390/v4010083
复制
发表时间：
2012-01
期刊：
影响因子：
--
通讯作者：
York J
中科院分区：
文献类型：
--
作者：
Nunberg JH;York J
ArenaVirus包括一个不同的包膜负链RNA病毒家族，这些病毒是全世界特定啮齿动物宿主的地方性病毒。几种阿拉伯病毒会引起人类的严重出血热，包括南美洲的Junín和Machupo病毒以及西非的拉沙热病毒。ArenaVirus进入宿主细胞是由包膜糖蛋白复合体GPC介导的。病毒粒子被内吞，结合到细胞表面的受体上，膜融合是对内小体的生理性酸化做出的反应。与其他I类病毒融合蛋白一样，GPC介导的膜融合是通过一系列受调控的构象变化促进的，从而形成经典的融合后发夹三聚体结构。然而，GPC在I类融合蛋白中是独一无二的，因为成熟的复合体除了典型的受体结合和融合蛋白外，还保留了一个稳定的信号肽(SSP)作为第三亚单位。我们将回顾三方GPC复合体的奇怪性质，并描述SSP与融合亚单位相互作用以调节pH诱导的膜融合激活的证据。这种在病毒粒子上保持GPC亚稳定预融合状态并在酸性pH下激活I类融合级联的不同寻常的解决方案为抗病毒干预提供了新的靶点。
Arenaviruses comprise a diverse family of enveloped negative-strand RNA viruses that are endemic to specific rodent hosts worldwide. Several arenaviruses cause severe hemorrhagic fevers in humans, including Junín and Machupo viruses in South America and Lassa fever virus in western Africa. Arenavirus entry into the host cell is mediated by the envelope glycoprotein complex, GPC. The virion is endocytosed on binding to a cell-surface receptor, and membrane fusion is initiated in response to physiological acidification of the endosome. As with other class I virus fusion proteins, GPC-mediated membrane fusion is promoted through a regulated sequence of conformational changes leading to formation of the classical postfusion trimer-of-hairpins structure. GPC is, however, unique among the class I fusion proteins in that the mature complex retains a stable signal peptide (SSP) as a third subunit, in addition to the canonical receptor-binding and fusion proteins. We will review the curious properties of the tripartite GPC complex and describe evidence that SSP interacts with the fusion subunit to modulate pH-induced activation of membrane fusion. This unusual solution to maintaining the metastable prefusion state of GPC on the virion and activating the class I fusion cascade at acidic pH provides novel targets for antiviral intervention.
登录
查看更多内容
影响因子：
11.8
作者：
Amorosa, Valerianna;MacNeil, Adam;Nichol, Stuart T.
通讯作者：
Nichol, Stuart T.
影响因子：
64.5
作者：
Cheng, Y;Zak, O;Walz, T
通讯作者：
Walz, T
影响因子：
6.7
作者：
Abraham, Jonathan;Kwong, Jo Ann;Choe, Hyeryun
通讯作者：
Choe, Hyeryun
影响因子：
3.7
作者：
Coulibaly-N'Golo D;Allali B;Kouassi SK;Fichet-Calvet E;Becker-Ziaja B;Rieger T;Olschläger S;Dosso H;Denys C;Ter Meulen J;Akoua-Koffi C;Günther S
通讯作者：
Günther S
影响因子：
7.6
作者：
Bolken TC;Laquerre S;Zhang Y;Bailey TR;Pevear DC;Kickner SS;Sperzel LE;Jones KF;Warren TK;Amanda Lund S;Kirkwood-Watts DL;King DS;Shurtleff AC;Guttieri MC;Deng Y;Bleam M;Hruby DE
通讯作者：
Hruby DE