Epstein–Barr virus (EBV), a member of the Herpesviridae family, maintains a lifelong latent infection in human B cells. Switching from the latent to the lytic phase of its lifecycle allows the virus to replicate and spread. The viral lytic cycle is induced in infected cultured cells by drugs such as sodium butyrate and azacytidine. Lytic reactivation can be inhibited by natural products and pharmaceuticals. The anticonvulsant drugs valproic acid and valpromide inhibit EBV in Burkitt lymphoma cells. Therefore, other drugs that treat neurological and psychological disorders were investigated for effects on EBV lytic reactivation. Clozapine, an atypical antipsychotic drug used to treat schizophrenia and bipolar disorder, was found to inhibit the reactivation of the EBV lytic cycle. Levels of the viral lytic genes BZLF1, BRLF1, and BMLF1 were decreased by treatment with clozapine in induced Burkitt lymphoma cells. The effects on viral gene expression were dependent on the dose of clozapine, yet cells were viable at an inhibitory concentration of clozapine. One metabolite of clozapine—desmethylclozapine—also inhibited EBV lytic reactivation, while another metabolite—clozapine-N-oxide—had no effect. These drugs may be used to study cellular pathways that control the viral lytic switch in order to develop treatments for diseases caused by EBV.
The Epstein‐Barr Virus (EBV) is a member of the herpes virus family and causes infectious mononucleosis. Epstein‐Barr Virus was the first virus discovered to cause cancer in humans. After infection with EBV, the virus maintains a lifelong dormant infection within the host. The virus's life cycle consists of two phases, the latent and the lytic phase. The latent phase allows the virus to lie dormant within the host without presenting any symptoms, while during the lytic phase the virus reproduces and spreads among cells. The virus switches between the latent and lytic phases in response to environmental stimuli, including some pharmaceuticals. We investigated the response of the virus to atypical antipsychotic drugs. Antipsychotic drugs are used to treat conditions such as schizophrenia and bipolar disorder. Atypical antipsychotics, also known as second generation antipsychotics, have a different chemical structure and are generally more effective than the typical (first generation) antipsychotics. The effects of varying concentrations of the drugs on the reactivation of EBV into the lytic cycle were tested. The degree of viral reactivation was measured by expression of the viral BZLF1 gene, a regulatory gene expressed during reactivation into the Epstein‐Barr Virus lytic cycle. Quantitative polymerase chain reaction (qPCR) monitored BZLF1 gene expression. Expression of the BZLF1 gene and viral reactivation was found to be inhibited. Understanding the conditions and cellular pathways that inhibit the lytic phase of the virus will help to better understand the virus's life cycle in order to develop treatments for cancers caused by Epstein‐Barr Virus.Support or Funding InformationThis work was funded by the UWL College of Science and Health, UWL Faculty Research Grants to KLG, and Undergraduate Research and Creativity grants to AGA.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.