Functional Diversity: Update of the Posttranslational Modification of Epstein-Barr Virus Coding Proteins

Overview

Journal Cell Mol Life Sci

Publisher Springer

Specialty Biology

Date 2022 Nov 14

PMID 36376593

Authors

Yujie Sun

Wen Liu

Bing Luo

Affiliations

Soon will be listed here.

Abstract

Epstein-Barr virus (EBV), a human oncogenic herpesvirus with a typical life cycle consisting of latent phase and lytic phase, is associated with many human diseases. EBV can express a variety of proteins that enable the virus to affect host cell processes and evade host immunity. Additionally, these proteins provide a basis for the maintenance of viral infection, contribute to the formation of tumors, and influence the occurrence and development of related diseases. Posttranslational modifications (PTMs) are chemical modifications of proteins after translation and are very important to guarantee the proper biological functions of these proteins. Studies in the past have intensely investigated PTMs of EBV-encoded proteins. EBV regulates the progression of the latent phase and lytic phase by affecting the PTMs of its encoded proteins, which are critical for the development of EBV-associated human diseases. In this review, we summarize the PTMs of EBV-encoded proteins that have been discovered and studied thus far with focus on their effects on the viral life cycle.

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References

Gahn T, Sugden B . An EBNA-1-dependent enhancer acts from a distance of 10 kilobase pairs to increase expression of the Epstein-Barr virus LMP gene. J Virol. 1995; 69(4):2633-6. PMC: 188944. DOI: 10.1128/JVI.69.4.2633-2636.1995. View

Wang P, Day L, Dheekollu J, Lieberman P . A redox-sensitive cysteine in Zta is required for Epstein-Barr virus lytic cycle DNA replication. J Virol. 2005; 79(21):13298-309. PMC: 1262569. DOI: 10.1128/JVI.79.21.13298-13309.2005. View

Wimmer P, Schreiner S, Dobner T . Human pathogens and the host cell SUMOylation system. J Virol. 2011; 86(2):642-54. PMC: 3255802. DOI: 10.1128/JVI.06227-11. View

Chang P, Campbell M, Robertson E . Human Oncogenic Herpesvirus and Post-translational Modifications - Phosphorylation and SUMOylation. Front Microbiol. 2016; 7:962. PMC: 4911386. DOI: 10.3389/fmicb.2016.00962. View

El-Guindy A, Heston L, Delecluse H, Miller G . Phosphoacceptor site S173 in the regulatory domain of Epstein-Barr Virus ZEBRA protein is required for lytic DNA replication but not for activation of viral early genes. J Virol. 2007; 81(7):3303-16. PMC: 1866087. DOI: 10.1128/JVI.02445-06. View

Verweij F, de Heus C, Kroeze S, Cai H, Kieff E, Piersma S . Exosomal sorting of the viral oncoprotein LMP1 is restrained by TRAF2 association at signalling endosomes. J Extracell Vesicles. 2015; 4:26334. PMC: 4394166. DOI: 10.3402/jev.v4.26334. View

Houen G, Trier N . Epstein-Barr Virus and Systemic Autoimmune Diseases. Front Immunol. 2021; 11:587380. PMC: 7817975. DOI: 10.3389/fimmu.2020.587380. View

Fierti A, Bright Yakass M, Okertchiri E, Adadey S, Quaye O . The Role of Epstein-Barr Virus in Modulating Key Tumor Suppressor Genes in Associated Malignancies: Epigenetics, Transcriptional, and Post-Translational Modifications. Biomolecules. 2022; 12(1). PMC: 8773690. DOI: 10.3390/biom12010127. View

Baichwal V, Sugden B . Posttranslational processing of an Epstein-Barr virus-encoded membrane protein expressed in cells transformed by Epstein-Barr virus. J Virol. 1987; 61(3):866-75. PMC: 254031. DOI: 10.1128/JVI.61.3.866-875.1987. View

10.

Kwiatkowski B, Chen S, Schubach W . CKII site in Epstein-Barr virus nuclear protein 2 controls binding to hSNF5/Ini1 and is important for growth transformation. J Virol. 2004; 78(11):6067-72. PMC: 415811. DOI: 10.1128/JVI.78.11.6067-6072.2004. View

11.

Longnecker R, Druker B, Roberts T, Kieff E . An Epstein-Barr virus protein associated with cell growth transformation interacts with a tyrosine kinase. J Virol. 1991; 65(7):3681-92. PMC: 241385. DOI: 10.1128/JVI.65.7.3681-3692.1991. View

12.

Geiss-Friedlander R, Melchior F . Concepts in sumoylation: a decade on. Nat Rev Mol Cell Biol. 2007; 8(12):947-56. DOI: 10.1038/nrm2293. View

13.

Grasser F, Gottel S, Haiss P, Boldyreff B, Issinger O, Mueller-Lantzsch N . Phosphorylation of the Epstein-Barr virus nuclear antigen 2. Biochem Biophys Res Commun. 1992; 186(3):1694-701. DOI: 10.1016/s0006-291x(05)81604-3. View

14.

Feederle R, Klinke O, Kutikhin A, Poirey R, Tsai M, Delecluse H . Epstein-Barr Virus: From the Detection of Sequence Polymorphisms to the Recognition of Viral Types. Curr Top Microbiol Immunol. 2015; 390(Pt 1):119-48. DOI: 10.1007/978-3-319-22822-8_7. View

15.

Calderwood M, Holthaus A, Johannsen E . The Epstein-Barr virus LF2 protein inhibits viral replication. J Virol. 2008; 82(17):8509-19. PMC: 2519677. DOI: 10.1128/JVI.00315-08. View

16.

Hung S, Kang M, Kieff E . Maintenance of Epstein-Barr virus (EBV) oriP-based episomes requires EBV-encoded nuclear antigen-1 chromosome-binding domains, which can be replaced by high-mobility group-I or histone H1. Proc Natl Acad Sci U S A. 2001; 98(4):1865-70. PMC: 29348. DOI: 10.1073/pnas.98.4.1865. View

17.

Miller C, Burkhardt A, Lee J, Stealey B, Longnecker R, Bolen J . Integral membrane protein 2 of Epstein-Barr virus regulates reactivation from latency through dominant negative effects on protein-tyrosine kinases. Immunity. 1995; 2(2):155-66. DOI: 10.1016/s1074-7613(95)80040-9. View

18.

Sivachandran N, Cao J, Frappier L . Epstein-Barr virus nuclear antigen 1 Hijacks the host kinase CK2 to disrupt PML nuclear bodies. J Virol. 2010; 84(21):11113-23. PMC: 2953151. DOI: 10.1128/JVI.01183-10. View

19.

Calderwood M, Venkatesan K, Xing L, Chase M, Vazquez A, Holthaus A . Epstein-Barr virus and virus human protein interaction maps. Proc Natl Acad Sci U S A. 2007; 104(18):7606-11. PMC: 1863443. DOI: 10.1073/pnas.0702332104. View

20.

Chien K, Chang Y, Yu J, Fan L, Lee C, Chi L . Identification of a new in vivo phosphorylation site in the cytoplasmic carboxyl terminus of EBV-LMP1 by tandem mass spectrometry. Biochem Biophys Res Commun. 2006; 348(1):47-55. DOI: 10.1016/j.bbrc.2006.06.188. View