We previously reported a rickettsial heartwater-like disease in vipers from Ghana that resembled heartwater in its gross lesions, was apparently transmitted by ticks (Aponomma and Amblyomma), and responded clinically favorably to early treatment with tetracycline. Cell culture showed consistent cytopathic effects in bovine endothelial cells, viper cells, and mouse cells, and inhibition of cytopathic effect by tetracycline in vitro. A type D retrovirus was observed in vacuoles in all infected cells. The virus and rickettsia infection was associated with transfer of cytopathic effect, regardless of cell species. Close association of virus and rickettsia may indicate a dual infection etiology of viper plague.