Interferon Inducers in Therapy of Infection with Encephalomyocarditis Virus in Mice. I. Effect of Single Doses of Polyriboinosinic-Polyribocytidylic Acid and Tilorone Hydrochloride on Viral Pathogenesis

Abstract

Mice inoculated with encephalomyocarditis virus develop an infection [hat in many respects simulates human disease caused by enteroviruses. The effect of treatment with a single dose of either polyriboinosinic-polyribocytidylic acid (poly I: poly C) or tilorone hydrochloride on the pathogenesis of the infection with encephalomyocarditis virus in individual mice was correlated with the outcome of the disease in the same animals. Both poly I: poly C and tilorone protected animals from the lethal consequences of the disease when administered prophylactically but were progressively less effective as the infection developed. Successful treatment with either interferon inducer was characterized in every case by complete suppression of detectable viremia. The viremic phase of infection was partially suppressed or delayed by treatment, but detection of circulating virus was always followed by the death of the animal involved. Seeding and subsequent replication of the virus in a target organ (the central nervous system) apparently resulted from the viremia. These data indicate that, for treatment to be successful, the interferon inducer had to be administered sufficiently early during infection to prevent development of detectable viremia and subsequent seeding of target organs. The importance of examining samples from individual animals when investigating the alterations of pathogenesis associated with antiviral chemotherapy was also demonstrated.