Epstein-Barr Virus BGLF4 Kinase Induces Disassembly of the Nuclear Lamina To Facilitate Virion Production
Epstein-Barr Virus BGLF4 Kinase Induces Disassembly of the Nuclear Lamina To Facilitate Virion Production
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DOI：
10.1128/jvi.01100-08
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发表时间：
2008-12-01
影响因子：
5.4
通讯作者：
Chen, Mei-Ru
中科院分区：
文献类型：
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作者：
Lee, Chung-Pei;Huang, Yu-Hao;Chen, Mei-Ru
DNA病毒采用各种策略来调节细胞环境，以实现高效的基因组复制和病毒粒子的产生。先前，我们证实eb病毒（EBV） BGLF4激酶通过凝集蛋白和拓扑异构酶II α的激活诱导染色体过早凝集（李正平，陈家英，王家泰，Kimura K.， A. Takemoto, Lu C. C., Chen M. R.， J.病毒学报，81:566 -5180,2007）。在这项研究中，我们发现BGLF4在体外与lamin A/C相互作用并磷酸化lamin A蛋白。利用绿色荧光蛋白(GFP)-层粘胶蛋白a系统，我们发现层粘胶蛋白a的Ser-22、Ser-390和Ser-392在bglf4诱导的核层解体和EBV再激活介导的核层粘胶蛋白重新分配中起重要作用。GFP-lamin A（5A）在lamin A的22、390、392、652和657个氨基酸上有5个丝氨酸残基被Ala取代。我们的数据表明，BGLF4激酶磷酸化了lamin A/C，促进了核层的重组，从而可能促进了BFRF1和BFLF2s的相互作用和随后的病毒粒子成熟。α -和β -疱疹病毒的UL激酶也通过核层蛋白A/C上的相似位点诱导核层的分解，提示疱疹病毒核出口的保守机制。
DNA viruses adopt various strategies to modulate the cellular environment for efficient genome replication and virion production. Previously, we demonstrated that the BGLF4 kinase of Epstein-Barr virus (EBV) induces premature chromosome condensation through the activation of condensin and topoisomerase II alpha (C. P. Lee, J. Y. Chen, J. T. Wang, K. Kimura, A. Takemoto, C. C. Lu, and M. R. Chen, J. Virol. 81: 5166-5180, 2007). In this study, we show that BGLF4 interacts with lamin A/C and phosphorylates lamin A protein in vitro. Using a green fluorescent protein (GFP)-lamin A system, we found that Ser-22, Ser-390, and Ser-392 of lamin A are important for the BGLF4-induced disassembly of the nuclear lamina and the EBV reactivation-mediated redistribution of nuclear lamin. Virion production and protein levels of two EBV primary envelope proteins, BFRF1 and BFLF2, were reduced significantly by the expression of GFP-lamin A(5A), which has five Ser residues replaced by Ala at amino acids 22, 390, 392, 652, and 657 of lamin A. Our data indicate that BGLF4 kinase phosphorylates lamin A/C to promote the reorganization of the nuclear lamina, which then may facilitate the interaction of BFRF1 and BFLF2s and subsequent virion maturation. UL kinases of alpha-and betaherpesviruses also induce the disassembly of the nuclear lamina through similar sites on lamin A/C, suggesting a conserved mechanism for the nuclear egress of herpesviruses.