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Inhibition of Epstein-Barr Virus Lytic Reactivation by the Atypical Antipsychotic Drug Clozapine.
- Source :
-
Viruses [Viruses] 2019 May 17; Vol. 11 (5). Date of Electronic Publication: 2019 May 17. - Publication Year :
- 2019
-
Abstract
- 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.
- Subjects :
- Burkitt Lymphoma
Cell Line, Tumor
Clozapine analogs & derivatives
Clozapine chemistry
Dose-Response Relationship, Drug
Epstein-Barr Virus Infections virology
Gene Expression Regulation, Viral drug effects
Herpesvirus 4, Human genetics
Humans
Immediate-Early Proteins metabolism
Phosphoproteins metabolism
Trans-Activators metabolism
Virus Activation drug effects
Virus Latency genetics
Antipsychotic Agents antagonists & inhibitors
Clozapine antagonists & inhibitors
Herpesvirus 4, Human drug effects
Virus Latency drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1999-4915
- Volume :
- 11
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Viruses
- Publication Type :
- Academic Journal
- Accession number :
- 31108875
- Full Text :
- https://doi.org/10.3390/v11050450