Exploring the anti-EBV potential of suberoylanilide hydroxamic acid: Induction of apoptosis in infected cells through suppressing BART gene expression and inducing lytic infection.

Autor: Liu Y; Department of Microbiology, Faculty of Medicine, Shimane University, 89-1 Enya, Izumo, Shimane, 693-8501, Japan. Electronic address: m209431@med.shimane-u.ac.jp., Wai AP; Department of Microbiology, Faculty of Medicine, Shimane University, 89-1 Enya, Izumo, Shimane, 693-8501, Japan. Electronic address: aungpwai@med.shimane-u.ac.jp., Zolzaya T; Department of Microbiology, Faculty of Medicine, Shimane University, 89-1 Enya, Izumo, Shimane, 693-8501, Japan. Electronic address: zolzaya.tumurgan@med.shimane-u.ac.jp., Iida Y; Department of Immunology, Faculty of Medicine, Shimane University, 89-1 Enya, Izumo, Shimane, 693-8501, Japan. Electronic address: yiida@med.shimane-u.ac.jp., Okada S; Department of Microbiology, Faculty of Medicine, Shimane University, 89-1 Enya, Izumo, Shimane, 693-8501, Japan. Electronic address: s.okada@med.shimane-u.ac.jp., Iizasa H; Department of Microbiology, Faculty of Medicine, Shimane University, 89-1 Enya, Izumo, Shimane, 693-8501, Japan. Electronic address: iizasah@med.shimane-u.ac.jp., Yoshiyama H; Department of Microbiology, Faculty of Medicine, Shimane University, 89-1 Enya, Izumo, Shimane, 693-8501, Japan. Electronic address: yosiyama@med.shimane-u.ac.jp.
Jazyk: angličtina
Zdroj: Virology [Virology] 2024 Sep; Vol. 597, pp. 110161. Date of Electronic Publication: 2024 Jul 02.
DOI: 10.1016/j.virol.2024.110161
Abstrakt: Epstein-Barr virus (EBV) is linked to lymphoma and epithelioma but lacks drugs specifically targeting EBV-positive tumors. BamHI A Rightward Transcript (BART) miRNAs are expressed in all EBV-positive tumors, suppressing both lytic infection and host cell apoptosis. We identified suberoylanilide hydroxamic acid (SAHA), an inhibitor of histone deacetylase enzymes, as an agent that suppresses BART promoter activity and transcription of BART miRNAs. SAHA treatment demonstrated a more pronounced inhibition of cell proliferation in EBV-positive cells compared to EBV-negative cells, affecting both p53 wild-type and mutant gastric epithelial cells. SAHA treatment enhanced lytic infection in wild-type EBV-infected cells, while also enhancing cell death in BZLF1-deficient EBV-infected cells. It reduced BART gene expression by 85% and increased the expression of proapoptotic factors targeted by BART miRNAs. These findings suggest that SAHA not only induces lytic infection but also leads to cell death by suppressing BART miRNA transcription and promoting the apoptotic program.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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