Division of Molecular Virology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
J Virol. 2014 May;88(9):4657-67. doi: 10.1128/JVI.00137-14. Epub 2014 Feb 12.
Herpesviruses have evolved a unique mechanism for nuclear egress of nascent progeny nucleocapsids: the nucleocapsids bud through the inner nuclear membrane into the perinuclear space between the inner and outer nuclear membranes (primary envelopment), and enveloped nucleocapsids then fuse with the outer nuclear membrane to release nucleocapsids into the cytoplasm (de-envelopment). We have shown that the herpes simplex virus 1 (HSV-1) major virion structural protein UL47 (or VP13/VP14) is a novel regulator for HSV-1 nuclear egress. In particular, we demonstrated the following: (i) UL47 formed a complex(es) with HSV-1 proteins UL34, UL31, and/or Us3, which have all been reported to be critical for viral nuclear egress, and these viral proteins colocalized at the nuclear membrane in HSV-1-infected cells; (ii) the UL47-null mutation considerably reduced primary enveloped virions in the perinuclear space although capsids accumulated in the nucleus; and (iii) UL47 was detected in primary enveloped virions in the perinuclear space by immunoelectron microscopy. These results suggested that UL47 promoted HSV-1 primary envelopment, probably by interacting with the critical HSV-1 regulators for viral nuclear egress and by modulating their functions.
Like other herpesviruses, herpes simplex virus 1 (HSV-1) has evolved a vesicle-mediated nucleocytoplasmic transport mechanism for nuclear egress of nascent progeny nucleocapsids. Although previous reports identified and characterized several HSV-1 and cellular proteins involved in viral nuclear egress, complete details of HSV-1 nuclear egress remain to be elucidated. In this study, we have presented data suggesting (i) that the major HSV-1 virion structural protein UL47 (or VP13/VP14) formed a complex with known viral regulatory proteins critical for viral nuclear egress and (ii) that UL47 played a regulatory role in HSV-1 primary envelopment. Thus, we identified UL47 as a novel regulator for HSV-1 nuclear egress.
疱疹病毒进化出一种独特的机制，用于将新生子代核衣壳从核内输出：核衣壳通过内核膜芽生到内、外核膜之间的核周腔（初级包膜），然后包裹的核衣壳与外核膜融合，将核衣壳释放到细胞质中（脱包膜）。我们已经表明，单纯疱疹病毒 1（HSV-1）的主要病毒结构蛋白 UL47（或 VP13/VP14）是 HSV-1 核输出的新型调节因子。特别是，我们证明了以下几点：（i）UL47 与 HSV-1 蛋白 UL34、UL31 和/或 Us3 形成复合物，这些蛋白均被报道对病毒核输出至关重要，并且这些病毒蛋白在 HSV-1 感染的细胞中在核膜上共定位；（ii）UL47 缺失突变大大减少了核周腔中的初级包膜病毒，但衣壳在核内积累；（iii）免疫电子显微镜检测到 UL47 存在于核周腔中的初级包膜病毒中。这些结果表明，UL47 促进了 HSV-1 的初级包膜，可能是通过与病毒核输出的关键 HSV-1 调节因子相互作用，并调节它们的功能。
与其他疱疹病毒一样，单纯疱疹病毒 1（HSV-1）进化出一种囊泡介导的核质转运机制，用于新生子代核衣壳从核内输出。尽管先前的报道确定并描述了几种参与病毒核输出的 HSV-1 和细胞蛋白，但 HSV-1 核输出的完整细节仍有待阐明。在这项研究中，我们提供的数据表明（i）HSV-1 的主要病毒结构蛋白 UL47（或 VP13/VP14）与已知对病毒核输出至关重要的病毒调节蛋白形成复合物，（ii）UL47 在 HSV-1 的初级包膜中发挥调节作用。因此，我们确定 UL47 是 HSV-1 核输出的新型调节因子。
