Characterization and Intracellular Trafficking of Epstein-Barr Virus BBLF1, a Protein Involved in Virion Maturation
Characterization and Intracellular Trafficking of Epstein-Barr Virus BBLF1, a Protein Involved in Virion Maturation
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DOI：
10.1128/jvi.01126-12
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发表时间：
2012-09-01
影响因子：
5.4
通讯作者：
Hung, Chien-Hui
中科院分区：
文献类型：
--
作者：
Chiu, Ya-Fang;Sugden, Bill;Hung, Chien-Hui
EB病毒（EBV）BBLF 1与单纯疱疹病毒1型UL 11和巨细胞病毒UL 99被膜蛋白共有13%至15%的氨基酸序列同一性，其参与病毒成熟过程中的最终增殖。这项研究表明，BBLF 1是一种肉豆蔻酰化和棕榈酰化的蛋白质，UL 11和UL 99也是如此。BBLF 1的豆蔻酰化既促进其膜锚定又稳定其膜。BBLF 1被证明定位于沿着gp 350/220的反式高尔基体网络（trans-Golgi network，TGN），这是EBV颗粒发生最终沉积的位点。BBLF 1在TGN的定位需要豆蔻酰化和两个酸性簇，其与PACS-1（一种胞质蛋白）相互作用，以介导从内体到TGN的逆行转运。在EBV裂解性复制过程中BBLF 1表达的敲低降低了病毒颗粒的产生，证明了BBLF 1对实现病毒颗粒的最佳产生的需求。BBLF 1被假设为在病毒成熟期间促进被膜衣壳出芽到糖蛋白包埋的膜中。
Epstein-Barr virus (EBV) BBLF1 shares 13 to 15% amino acid sequence identities with the herpes simplex virus 1 UL11 and cytomegalovirus UL99 tegument proteins, which are involved in the final envelopment during viral maturation. This study demonstrates that BBLF1 is a myristoylated and palmitoylated protein, as are UL11 and UL99. Myristoylation of BBLF1 both facilitates its membrane anchoring and stabilizes it. BBLF1 is shown to localize to the trans-Golgi network (TGN) along with gp350/220, a site where final envelopment of EBV particles takes place. The localization of BBLF1 at the TGN requires myristoylation and two acidic clusters, which interact with PACS-1, a cytosolic protein, to mediate retrograde transport from the endosomes to the TGN. Knockdown of the expression of BBLF1 during EBV lytic replication reduces the production of virus particles, demonstrating the requirement of BBLF1 to achieve optimal production of virus particles. BBLF1 is hypothesized to facilitate the budding of tegumented capsid into glycoprotein-embedded membrane during viral maturation.