The ESCRT Machinery Is Recruited by the Viral BFRF1 Protein to the Nucleus-Associated Membrane for the Maturation of Epstein-Barr Virus

PLoS Pathogens

Po-Ting Liu¹  Mei-Tzu Su²  Chou-Wei Chang³  Huey-Huey Chua³  Ching-Hwa Tsai³  Hsiu-Ni Kung³  Chung-Pei Lee³  Yu-Hsin Chang³  Fu-Tong Liu³  Mei-Ru Chen⁴ 

[1] Center of General Education, National Taipei University of Nursing and Health Sciences, Taipei, Taiwan;Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei, Taiwan;Graduate Institute and Department of Microbiology, College of Medicine, National Taiwan University, Taipei, Taiwan;Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan

关键词: Nuclear membrane;    Vesicles;    Plasmid construction;    Transfection;    HeLa cells;    Viral packaging;    Cytoplasmic staining;    Viral replication;   

DOI  :  10.1371/journal.ppat.1002904

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

The cellular endosomal sorting complex required for transport (ESCRT) machinery participates in membrane scission and cytoplasmic budding of many RNA viruses. Here, we found that expression of dominant negative ESCRT proteins caused a blockade of Epstein-Barr virus (EBV) release and retention of viral BFRF1 at the nuclear envelope. The ESCRT adaptor protein Alix was redistributed and partially colocalized with BFRF1 at the nuclear rim of virus replicating cells. Following transient transfection, BFRF1 associated with ESCRT proteins, reorganized the nuclear membrane and induced perinuclear vesicle formation. Multiple domains within BFRF1 mediated vesicle formation and Alix recruitment, whereas both Bro and PRR domains of Alix interacted with BFRF1. Inhibition of ESCRT machinery abolished BFRF1-induced vesicle formation, leading to the accumulation of viral DNA and capsid proteins in the nucleus of EBV-replicating cells. Overall, data here suggest that BFRF1 recruits the ESCRT components to modulate nuclear envelope for the nuclear egress of EBV.

【 授权许可】

CC BY