Herpes simplex virus glycoproteins gB and gH function in fusion between the virion envelope and the outer nuclear membrane
Herpes simplex virus glycoproteins gB and gH function in fusion between the virion envelope and the outer nuclear membrane
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DOI：
10.1073/pnas.0703790104
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发表时间：
2007-06-12
影响因子：
11.1
通讯作者：
Johnson, David C.
中科院分区：
文献类型：
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作者：
Farnsworth, Aaron;Wisner, Todd W.;Johnson, David C.
疱疹病毒必须穿过核膜才能进入细胞质，并最终离开细胞。据信疱疹病毒核衣壳通过内核膜（NM）出芽进入核周空间。为了到达细胞质，这些包膜颗粒必须与外部 NM 和未包膜的衣壳融合，然后在跨高尔基体网络中获得第二个包膜。人们对疱疹病毒病毒粒子与外部 NM 融合的过程知之甚少。在这里，我们发现缺乏两种假定的融合糖蛋白 gB 和 gH 的单纯疱疹病毒 (HSV) 突变体无法穿过核膜。有包膜的病毒粒子积聚在核周空间或凸入核质的膜囊泡中（突出）。相比之下，仅缺乏 gB 或 gH 的突变体在核出口方面仅表现出较小的缺陷或没有缺陷。我们得出结论，HSV gB 或 gH 都可以促进病毒体包膜和外部 NM 之间的融合。值得注意的是，与 HSV 进入相关的融合需要 gB 和 gH 的协同作用，这表明两种类型的融合（外出与进入）是不同的过程。
Herpesviruses must traverse the nuclear envelope to gain access to the cytoplasm and, ultimately, to exit cells. It is believed that herpesvirus nucleocapsids enter the perinuclear space by budding through the inner nuclear membrane (NM). To reach the cytoplasm these enveloped particles must fuse with the outer NM and the unenveloped capsids then acquire a second envelope in the trans-Golgi network. Little is known about the process by which herpesviruses virions fuse with the outer NM. Here we show that a herpes simplex virus (HSV) mutant lacking both the two putative fusion glycoproteins gB and gH failed to cross the nuclear envelope. Enveloped virions accumulated in the perinuclear space or in membrane vesicles that bulged into the nucleoplasm (herniations). By contrast, mutants lacking just gB or gH showed only minor or no defects in nuclear egress. We concluded that either HSV gB or gH can promote fusion between the virion envelope and the outer NM. It is noteworthy that fusion associated with HSV entry requires the cooperative action of both gB and gH, suggesting that the two types of fusion (egress versus entry) are dissimilar processes.