The multiple sclerosis-associated retrovirus (MSRV), originally identified in cell cultures from patients with multiple sclerosis (MS), is closely related to the human endogenous retrovirus family W (HERV-W). Recently, HERV-W gag and env protein expression was demonstrated in MS lesions in situ. Here, the authors show that HERV-W gag and env proteins are induced by herpes simplex virus type 1 (HSV-1) in neuronal and brain endothelial cells in vitro. The transactivation of HERV-W proteins by HSV-1 could enhance their potential oligodendrotoxic and immunopathogenic effects, representing a mechanism by which HSV-1, and possibly also other herpesviruses associated with MS, may be linked to the pathogenesis of this disease.