title: Chaetocin reactivates the lytic replication of Epstein-Barr virus from latency via reactive oxygen species.
abstract: Oxidative stress, regarded as a negative effect of free radicals in vivo, takes place when organisms suffer from harmful stimuli. Some viruses can induce the release of reactive oxygen species (ROS) in infected cells, which may be closely related with their pathogenicity. In this report, chaetocin, a fungal metabolite reported to have antimicrobial and cytostatic activity, was studied for its effect on the activation of latent Epstein-Barr virus (EBV) in B95-8 cells. We found that chaetocin remarkably up-regulated EBV lytic transcription and DNA replication at a low concentration (50 nmol L-1). The activation of latent EBV was accompanied by an increased cellular ROS level. N-acetyl-L-cysteine (NAC), an ROS inhibitor, suppressed chaetocin-induced EBV activation. Chaetocin had little effect on histone H3K9 methylation, while NAC also significantly reduced H3K9 methylation. These results suggested that chaetocin reactivates latent EBV primarily via ROS pathways.
authors.affiliation: Department of Microbiology and Microbial Engineering, School of Life Sciences, Fudan University, Shanghai, 200438, China.
authors.forename: Shilun
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Microbiology and Microbial Engineering, School of Life Sciences, Fudan University, Shanghai, 200438, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Yin
authors.affiliation: Department of Microbiology and Microbial Engineering, School of Life Sciences, Fudan University, Shanghai, 200438, China. jzhong@fudan.edu.cn.
authors.forename: Jiang
authors.initials: J
authors.lastname: Zhong
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D000956:Antigens, Viral / Q000235:genetics / Q000378:metabolism; D001402:B-Lymphocytes / Q000187:drug effects / Q000378:metabolism / Q000821:virology; D015153:Blotting, Western; D002144:Callithrix; D002461:Cell Line, Transformed; D004305:Dose-Response Relationship, Drug; D016166:Free Radical Scavengers / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D005979:Glutathione Peroxidase / Q000235:genetics / Q000378:metabolism; D004854:Herpesvirus 4, Human / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D006657:Histones / Q000378:metabolism; D054884:Host-Pathogen Interactions / Q000187:drug effects; D006801:Humans; D008239:Lysine / Q000378:metabolism; D008745:Methylation / Q000187:drug effects; D009245:NADH Dehydrogenase / Q000235:genetics / Q000378:metabolism; D000080662:Phospholipid Hydroperoxide Glutathione Peroxidase; D010879:Piperazines / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014775:Virus Activation / Q000187:drug effects / Q000235:genetics; D017735:Virus Latency / Q000187:drug effects / Q000235:genetics; D014779:Virus Replication / Q000187:drug effects* / Q000235:genetics
chemical_list: D000956:Antigens, Viral; C063676:BZLF1 protein, Herpesvirus 4, Human; C083204:Epstein-Barr virus early antigen diffuse component; D016166:Free Radical Scavengers; D006657:Histones; D010879:Piperazines; D017382:Reactive Oxygen Species; D015534:Trans-Activators; C002511:chaetocin; D000080662:Phospholipid Hydroperoxide Glutathione Peroxidase; D005979:Glutathione Peroxidase; D009245:NADH Dehydrogenase; D008239:Lysine; D000111:Acetylcysteine
keywords: Epstein-Barr virus; chaetocin; reactive oxygen species