Subcellular Localization of Epstein–Barr Virus BLLF2 and Its Underlying Mechanisms

Jingjing Li, Yingjie Guo, Yangxi Deng, Li Hu, Bolin Li, Shenyu Deng, Jiayi Zhong, Li Xie, Shaoxuan Shi, Xuejun Hong, Xuelong Zheng, Mingsheng Cai (+1 others)
2021 Frontiers in Microbiology  
Epstein–Barr virus (EBV), the pathogen of several human malignancies, encodes many proteins required to be transported into the nucleus for viral DNA reproduction and nucleocapsids assembly in the lytic replication cycle. Here, fluorescence microscope, mutation analysis, interspecies heterokaryon assays, co-immunoprecipitation assay, RNA interference, and Western blot were performed to explore the nuclear import mechanism of EBV encoded BLLF2 protein. BLLF2 was shown to be a nucleocytoplasmic
more » ... uttling protein neither by a chromosomal region maintenance 1 (CRM1)- nor by a transporter associated with antigen processing (TAP)-dependent pathway. Yet, BLLF2's two functional nuclear localization signals (NLSs), NLS1 (16KRQALETVPHPQNRGR31) and NLS2 (44RRPRPPVAKRRRFPR58), were identified, whereas the predicted NES was nonfunctional. Finally, BLLF2 was proven to transport into the nucleus via a Ran-dependent and importin β1-dependent pathway. This mechanism may contribute to a more extensive insight into the assembly and synthesis of EBV virions in the nucleus, thus affording a new direction for the treatment of viruses.
doi:10.3389/fmicb.2021.672192 fatcat:aq6xqvikmjebta6737eesblxpe