The <i>In Vivo</i> Antiviral Effect of CL246,738 is Mediated by the Independent Induction of Interferon-α and Interferon-β

Abstract

An interferon (IFN) inducer and immunomodulator, CL246,738 [3,6-bis(2-piperidinoethoxy)acridine trihydrochloride], protected mice from lethal infection with Semliki Forest (SFV) and Banzi (BZV) viruses. A single oral dose of CL246,738 (5-150 mg/kg) administered 24 h before intraperitoneal challenge with SFV or BZV fully protected mice from lethal infection. Dose-dependent levels of circulating IFN peaked at 24 h in the serum and peritoneal fluid of CL246,738-treated mice. The circulating IFN of CL246,738-treated mice consisted of IFN-alpha and was produced by spleen cells. Peritoneal exudate cells (PEC) obtained from CL246,738-treated mice produced IFN-beta. Treatment in vivo with anti-IFN-alpha/beta and anti-IFN-beta reversed the protective effect of CL246,738 against lethal SFV encephalitis.