The effects of gamma interferon on replication of foot-and-mouth disease virus in persistently infected bovine cells

Foot-and-mouth disease virus (FMDV) causes a highly contagious viral disease of cloven-hoofed animals, which has a considerable socio-economic impact on the countries affected. In addition, persistent infection can occur following clinical or sub-clinical disease in either vaccinated or non-vaccinated cattle. The mechanism(s) by which FMDV persistence is established and maintained is not fully understood. To better understand the basic mechanisms controlling the virus infection in cattle, the effects of interferon gamma (IFN-gamma) on the replication of FMDV was evaluated in vitro in persistently infected-epithelial cells isolated from FMDV infected cattle. Initially primary bovine thyroid (BTY) cells were treated with varying doses of bovine recombinant IFN-gamma. The cytokine activity was measured by detection of viral antigen in cell supernatants and viral RNA expression compared with cells without INF-gamma treatment. Pretreatment with IFN-gamma profoundly affected FMDV growth in BTY cells. The replication of FMDV was affected in the presence of more than 2.5 u/ml of IFN-gamma and the effect was both dose-dependent and related to the time of exposure. Analysis of the mechanism of inhibition suggests that IFN-gamma did not inhibit the viral replication through induction of nitric oxide. More interesting is the finding that continuous treatment with IFN-gamma severely restricts FMDV replication or even cures persistently infected bovine epithelial cells, indicating that a cytokine-mediated pathway may be involved in the in vivo clearance of persistent FMDV.