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

Overview

Journal Front Microbiol

Specialty Microbiology

Date 2021 Aug 9

PMID 34367081

Citations 3

Authors

Jingjing Li

Yingjie Guo

Yangxi Deng

Li Hu

Bolin Li

Shenyu Deng

Jiayi Zhong

Li Xie

Shaoxuan Shi

Xuejun Hong

Xuelong Zheng

Mingsheng Cai

Meili Li

Affiliations

Soon will be listed here.

Abstract

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 shuttling 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 (KRQALETVPHPQNRGR) and NLS2 (RRPRPPVAKRRRFPR), were identified, whereas the predicted NES was nonfunctional. Finally, BLLF2 was proven to transport into the nucleus 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.

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