Hung Chien-Hui, Chiu Ya-Fang, Wang Wen-Hung, Chen Lee-Wen, Chang Pey-Jium, Huang Tsung-Yu, Lin Ying-Ju, Tsai Wan-Ju, Yang Chia-Ching
Graduate Institute of Clinical Medical Sciences, Chang-Gung University, Taoyuan, Taiwan.
Division of Infectious Diseases, Chang Gung Memorial Hospital Chiayi Branch, Chiayi, Taiwan.
Front Microbiol. 2020 Jan 24;10:3021. doi: 10.3389/fmicb.2019.03021. eCollection 2019.
BGLF2 is a tegument protein of the Epstein-Barr virus (EBV). This study finds that BGLF2 is expressed in the late stage of the EBV lytic cycle. Microscopic investigations reveal that BGLF2 is present in both the nucleus and the cytoplasm and colocalized with BBLF1 and gp350 at juxtanuclear regions in the cytoplasm. This study also finds that the basic KKK motif of BGLF2 and acidic DYEE motif of BBLF1 are crucial for the interaction between BGLF2 and BBLF1, which is required for the recruitment of BGLF2 to the BBLF1 that is anchored on the -Golgi-network (TGN). In addition, BGLF2 in a density gradient is co-sedimented with un-enveloped capsids, revealing that BGLF2 associates with the EBV capsid before the final envelopment. The knockout of BGLF2 expression is demonstrated to reduce the numbers of infectious virions that are released into the culture medium, but they do not affect the expression of lytic proteins and viral DNA replication. The production of infectious viral particles by a BGLF2-knockout mutant can be rescued by exogenously expressed BGLF2 but only partially rescued by BGLF2-3KA, which is a mutant with reduced ability to interact with BBLF1 but does not affect its ability to activate the MAPK pathway and the expression of the EBV lytic proteins, suggesting that the interaction of BGLF2 with BBLF1 is important to the efficient production of infectious viral particles during the maturation. The results of this study improve our understanding of how BGLF2 promotes EBV viral production.
BGLF2是爱泼斯坦-巴尔病毒（EBV）的一种被膜蛋白。本研究发现BGLF2在EBV裂解周期的后期表达。显微镜检查显示，BGLF2存在于细胞核和细胞质中，并与BBLF1和gp350在细胞质中的近核区域共定位。本研究还发现，BGLF2的碱性KKK基序和BBLF1的酸性DYEE基序对于BGLF2与BBLF1之间的相互作用至关重要，而这种相互作用是将BGLF2招募到锚定在反式高尔基体网络（TGN）上的BBLF1所必需的。此外，密度梯度中的BGLF2与无包膜的衣壳共同沉淀，表明BGLF2在最终包膜形成之前与EBV衣壳相关联。BGLF2表达的敲除被证明会减少释放到培养基中的感染性病毒粒子的数量，但它们不影响裂解蛋白的表达和病毒DNA复制。BGLF2敲除突变体产生感染性病毒颗粒的能力可以通过外源性表达的BGLF2得到挽救，但只能被BGLF2-3KA部分挽救，BGLF2-3KA是一种与BBLF1相互作用能力降低但不影响其激活MAPK途径和EBV裂解蛋白表达能力的突变体，这表明BGLF2与BBLF1的相互作用对于成熟过程中感染性病毒颗粒的有效产生很重要。本研究结果增进了我们对BGLF2如何促进EBV病毒产生的理解。
