Herpes Simplex Virus 1 UL31 and UL34 Gene Products Promote the Late Maturation of Viral Replication Compartments to the Nuclear Periphery
Herpes Simplex Virus 1 UL31 and UL34 Gene Products Promote the Late Maturation of Viral Replication Compartments to the Nuclear Periphery
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DOI：
10.1128/jvi.78.11.5591-5600.2004
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发表时间：
2004-06
影响因子：
5.4
通讯作者：
M. Simpson-Holley;J. Baines;R. Roller;D. Knipe
中科院分区：
文献类型：
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作者：
M. Simpson-Holley;J. Baines;R. Roller;D. Knipe
摘要
单纯疱疹病毒1型（HSV - 1）在宿主细胞核内形成复制区室（RCs），病毒DNA复制、晚期基因转录和衣壳化在此区域内发生。这些区域的形成导致宿主细胞染色质压缩和边缘化，在病毒RCs周围形成一个致密层，对病毒的核出芽或内核膜处的初次包膜形成潜在障碍。染色质层周围是核纤层，这是病毒出芽的又一宿主细胞屏障。在本研究中，我们描述了RC成熟的一个额外阶段，该阶段涉及宿主染色质和核纤层的破坏，以便RC能够接近核膜。在此阶段，染色质层的结构发生改变，它不再在RCs周围形成连续的层，而是碎片化，形成一些“岛”，RCs在这些“岛”之间延伸至核周边。与这些变化同时发生的是，核纤层成分 lamin A/C和lamin - 相关蛋白2似乎通过一种涉及UL31和UL34基因产物的机制重新分布。UL31或UL34基因缺失的病毒无法经历染色质重组和核纤层改变的这一阶段，而是形成被完整的宿主细胞染色质层和核纤层包围的RCs。我们推测，染色质结构调整和核纤层重组方面的这些缺陷解释了先前记录的这些突变病毒的生长缺陷。
ABSTRACT Herpes simplex virus 1 (HSV-1) forms replication compartments (RCs), domains in which viral DNA replication, late-gene transcription, and encapsidation take place, in the host cell nucleus. The formation of these domains leads to compression and marginalization of host cell chromatin, which forms a dense layer surrounding the viral RCs and constitutes a potential barrier to viral nuclear egress or primary envelopment at the inner nuclear membrane. Surrounding the chromatin layer is the nuclear lamina, a further host cell barrier to egress. In this study, we describe an additional phase in RC maturation that involves disruption of the host chromatin and nuclear lamina so that the RC can approach the nuclear envelope. During this phase, the structure of the chromatin layer is altered so that it no longer forms a continuous layer around the RCs but instead is fragmented, forming islands between which RCs extend to reach the nuclear periphery. Coincident with these changes, the nuclear lamina components lamin A/C and lamin-associated protein 2 appear to be redistributed via a mechanism involving the UL31 and UL34 gene products. Viruses in which the UL31 or UL34 gene has been deleted are unable to undergo this phase of chromatin reorganization and lamina alterations and instead form RCs which are bounded by an intact host cell chromatin layer and nuclear lamina. We postulate that these defects in chromatin restructuring and lamina reorganization explain the previously documented growth defects of these mutant viruses.