0 105

Cited 2 times in

Pharmacologic Activation of Lytic Epstein-Barr Virus Gene Expression without Virion Production

Authors
 Jaeyeun Lee  ;  John G. Kosowicz  ;  S. Diane Hayward  ;  Prashant Desai  ;  Jennifer Stone  ;  Jae Myun Lee  ;  Jun O. Liu  ;  Richard F. Ambinder 
Citation
 JOURNAL OF VIROLOGY, Vol.93(20) : e00998-19, 2019 
Journal Title
 JOURNAL OF VIROLOGY 
ISSN
 0022-538X 
Issue Date
2019
Keywords
Epstein-Barr virus ; gastric carcinoma ; integrated stress response ; lymphoma ; nasopharyngeal carcinoma ; oncolytic viruses ; proteasome ; unfolded protein response
Abstract
Several therapeutic strategies targeting Epstein-Barr virus (EBV)-associated tumors involve upregulation of viral lytic gene expression. Evidence has been presented that the unfolded protein response (UPR) leads to EBV lytic gene expression. Clofoctol, an antibacterial antibiotic, has been reported to upregulate the UPR in prostate cancer cell lines and to slow their growth. We investigated the effects of clofoctol on an EBV-positive Burkitt lymphoma cell line and confirmed the upregulation of all three branches of the UPR and activation of EBV lytic gene expression. While immediate early, early, and late EBV RNAs were all upregulated, immediate early and early viral proteins but not late viral proteins were expressed. Furthermore, infectious virions were not produced. The use of clofoctol in combination with a protein kinase R-like endoplasmic reticulum kinase inhibitor led to expression of late viral proteins. The effects of clofoctol on EBV lytic protein upregulation were not limited to lymphoid tumor cell lines but also occurred in naturally infected epithelial gastric cancer and nasopharyngeal cancer cell lines. An agent that upregulates lytic viral protein expression but that does not lead to the production of infectious virions may have particular value for lytic induction strategies in the clinical setting.IMPORTANCE Epstein-Barr virus is associated with many different cancers. In these cancers the viral genome is predominantly latent; i.e., most viral genes are not expressed, most viral proteins are not synthesized, and new virions are not produced. Some strategies for treating these cancers involve activation of lytic viral gene expression. We identify an antibacterial antibiotic, clofoctol, that is an activator of EBV lytic RNA and protein expression but that does not lead to virion production.
Full Text
https://jvi.asm.org/content/93/20/e00998-19.long
DOI
10.1128/JVI.00998-19
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Microbiology (미생물학교실) > 1. Journal Papers
Yonsei Authors
Lee, Jae Myun(이재면) ORCID logo https://orcid.org/0000-0002-5273-3113
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/174546
사서에게 알리기
  feedback

qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse

Links