Reactivation of Epstein–Barr virus by a dual-responsive fluorescent EBNA1-targeting agent with Zn2+-chelating function

Jiang, Lijun; Lung, Hong Lok; Huang, Tao; Lan, Rongfeng; Zha, Shuai; Chan, Lai Sheung; Thor, Waygen; Tsoi, Tik-Hung; Chau, Ho-Fai; Boreström, Cecilia; Cobb, Steven L.; Tsao, Sai Wah; Bian, Zhao-Xiang; Law, Ga-Lai; Wong, Wing-Tak; Tai, William Chi-Shing; Chau, Wai Yin; Du, Yujun; Tang, Lucas Hao Xi; Chiang, Alan Kwok Shing; Middeldorp, Jaap M.; Lo, Kwok-Wai; Mak, Nai Ki; Long, Nicholas J.; Wong, Ka-Leung

doi:10.1073/pnas.1915372116

Reactivation of Epstein–Barr virus by a dual-responsive fluorescent EBNA1-targeting agent with Zn2+-chelating function

Jiang, Lijun; Lung, Hong Lok; Huang, Tao; Lan, Rongfeng; Zha, Shuai; Chan, Lai Sheung; Thor, Waygen; Tsoi, Tik-Hung; Chau, Ho-Fai; Boreström, Cecilia; Cobb, Steven L.; Tsao, Sai Wah; Bian, Zhao-Xiang; Law, Ga-Lai; Wong, Wing-Tak; Tai, William Chi-Shing; Chau, Wai Yin; Du, Yujun; Tang, Lucas Hao Xi; Chiang, Alan Kwok Shing; Middeldorp, Jaap M.; Lo, Kwok-Wai; Mak, Nai Ki; Long, Nicholas J.; Wong, Ka-Leung

Authors

Lijun Jiang

Hong Lok Lung

Tao Huang

Rongfeng Lan

Shuai Zha

Lai Sheung Chan

Waygen Thor

Tik-Hung Tsoi

Ho-Fai Chau

Cecilia Boreström

Professor Steven Cobb s.l.cobb@durham.ac.uk
Professor

Sai Wah Tsao

Zhao-Xiang Bian

Ga-Lai Law

Wing-Tak Wong

William Chi-Shing Tai

Wai Yin Chau

Yujun Du

Lucas Hao Xi Tang

Alan Kwok Shing Chiang

Jaap M. Middeldorp

Kwok-Wai Lo

Nai Ki Mak

Nicholas J. Long

Ka-Leung Wong

Abstract

EBNA1 is the only Epstein–Barr virus (EBV) latent protein responsible for viral genome maintenance and is expressed in all EBV-infected cells. Zn2+ is essential for oligomerization of the functional EBNA1. We constructed an EBNA1 binding peptide with a Zn2+ chelator to create an EBNA1-specific inhibitor (ZRL5P4). ZRL5P4 by itself is sufficient to reactivate EBV from its latent infection. ZRL5P4 is able to emit unique responsive fluorescent signals once it binds with EBNA1 and a Zn2+ ion. ZRL5P4 can selectively disrupt the EBNA1 oligomerization and cause nasopharyngeal carcinoma (NPC) tumor shrinkage, possibly due to EBV lytic induction. Dicer1 seems essential for this lytic reactivation. As can been seen, EBNA1 is likely to maintain NPC cell survival by suppressing viral reactivation.

Citation

Jiang, L., Lung, H. L., Huang, T., Lan, R., Zha, S., Chan, L. S., Thor, W., Tsoi, T.-H., Chau, H.-F., Boreström, C., Cobb, S. L., Tsao, S. W., Bian, Z.-X., Law, G.-L., Wong, W.-T., Tai, W. C.-S., Chau, W. Y., Du, Y., Tang, L. H. X., Chiang, A. K. S., …Wong, K.-L. (2019). Reactivation of Epstein–Barr virus by a dual-responsive fluorescent EBNA1-targeting agent with Zn2+-chelating function. Proceedings of the National Academy of Sciences, 116(52), 26614-26624. https://doi.org/10.1073/pnas.1915372116

Journal Article Type	Article
Online Publication Date	Dec 10, 2019
Publication Date	Dec 26, 2019
Deposit Date	Jan 15, 2020
Publicly Available Date	Jan 15, 2020
Journal	Proceedings of the National Academy of Sciences
Print ISSN	0027-8424
Electronic ISSN	1091-6490
Publisher	National Academy of Sciences
Peer Reviewed	Peer Reviewed
Volume	116
Issue	52
Pages	26614-26624
DOI	https://doi.org/10.1073/pnas.1915372116
Public URL	https://durham-repository.worktribe.com/output/1278786