Ivermectin antiviral activity against Varicellovirus bovinealpha 1: assessment of intracellular drug accumulation in virus-infected cells

Abstract

Varicellovirus bovinealpha 1 (formerly bovine alphaherpesvirus type 1, BoAHV-1) is associated with several syndromesin cattle, including respiratory disease and is one of the main agents involved in the bovine respiratory disease complex(BRDC). Its infectious cycle is characterized by latent infections with sporadic virus reactivation and transmission. Althoughthe acute disease can be prevented by the use of vaccines, specifc therapeutic measures are not available. Ivermectin (IVM)is a semi-synthetic avermectin with a broad-spectrum antiparasitic activity, which has previously shown to have potential asan antiviral drug. In this study, IVM antiviral activity against BoAHV-1 was characterized in two cell lines (MDBK [MadinDarby bovine kidney] and BT [bovine turbinate]), including the measurement of intracellular drug accumulation withinvirus-infected cells. IVM antiviral activity was assessed at three diferent drug concentrations (1.25, 2.5 and 5 µM) afterincubation for 24, 48 and 72 h. Slight cytotoxicity was only observed with 5 µM IVM. Even the lowest IVM dose was able toinduce a signifcant reduction in virus titers in both cell lines. These fndings indicate that the antiviral efects of IVM wereevident in our experimental model within the range of concentrations achievable through therapeutic in vivo administration.Consequently, additional in vivo trials are necessary to validate the potential utility of these results in efectively managingBoAHV-1 in infected cattle.