Intranasal Challenge of Mice with Herpes Simplex Vims: An Experimental Model for Evaluation of the Efficacy of Antiviral Drugs

Abstract

An experimental model of herpetic infection based on intranasal challenge of 12-day-old mice with herpes simplex virus (type 1) has been developed for assessment of the efficacy of a variety of antiviral compounds with clinical potential: cytosine arabinoside, adenine arabinoside, iododeoxyuridine, ribavirin, chloriteoxidized oxyamylose, polyriboinosinic-polyribocytidylic acid, and interferon. The model employed is reminiscent of herpetic encephalitis in humans in both the portal of entry (nasopharyngeal cavity) and the mode of transmission (nerve route) of the virus to the target organ (brain). The mortality rate from viral infection was significantly reduced (greater than or equal to 30%) by the following treatment regimens: cytosine arabinoside, adenine arabinoside, iododeoxyuridine, and ribavirin, administered daily for seven consecutive days starting immediately after inoculation of virus, at dosage levels of 4-20 mg/kg, 20-100mg/kg, 100mg/kg, and 20-100 mg/kg, respectively; and chlorite-oxidized oxyamylose, polyriboinosinic-polyribocytidylic acid, and mouse interferon, administered 24 hr before viral challenge, as single doses of 100-500 mg/kg, 20mg/kg, and 10(7)-10(8) international reference units/kg respectively. Similar doses of polyriboinosinic-polyribocytidylic acid and mouse interferon administered after inoculation of virus did not alter the final mortality rate.