Inhibition of Epstein‐Barr Virus by Serotonin‐Dopamine Antagonists

Epstein‐Barr Virus (EBV), a herpesvirus family member, was the first human cancer‐associated virus discovered. EBV maintains a lifelong latent infection within the host B cells. During periodic reactivation into the lytic phase, the virus replicates and spreads among cells. The virus is reactivated into the lytic phase in response to environmental stress conditions. In cultured EBV‐positive cells, the lytic switch can be initiated by the addition of a variety of small‐molecule inducing agents. Viral reactivation is inhibited by diverse natural products and pharmaceuticals. Viral reactivation can be induced, or blocked, through a number of different mechanisms. Since one viral inhibitor is also a drug used to treat neurological conditions, we investigated the response of the virus to atypical antipsychotic drugs. Previously, we discovered clozapine is an inhibitor of EBV reactivation. Here we screened a panel of atypical antipsychotic drugs for effects on the expression of the viral lytic gene BZLF1. We found antagonists of serotonin and dopamine receptors inhibited the EBV lytic cycle in Burkitt lymphoma cells. The inhibitors may be functioning through their associated receptors or through any of their off target signaling pathways. These results highlight the lesser known roles of serotonin and dopamine signaling outside the central nervous system. Inhibition of EBV through novel mechanisms will be useful in elucidating the natural pathways of viral reactivation and in the treatment of EBV‐associated diseases. Support or Funding Information This work was funded by the UWL College of Science and Health and UWL Faculty Research Grants to KLG.