Treatment of Herpes Simplex Virus Types 1 and 2 Encephalitis in Mice with 9-β- d -Arabinofuranosyladenine

Abstract

The susceptibility of herpes simplex type 1 and type 2 viruses to 9-β- d -arabinofuranosyladenine (ara-A) was tested in intracerebrally infected mice. Subcutaneously administered ara-A resulted in markedly equivalent and reproducible chemotherapeutic activity against both serotypes of herpes simplex viruses. Administration of ara-A by several different intermittent dosage regimens showed that change in pattern of response in terms of survivors appears to be influenced more by total amount of drug administered than by schedule or duration of drug treatment. In general, surviving drug-treated, virus-infected animals survived rechallenge with 1,000 LD 50 of the respective homologous virus inoculated intracerebrally on the 21st day after the initial virus inoculation. A neutralization test performed in vitro-in vivo confirmed the identity of the two distinct serotypes of herpes simplex virus employed. The data indicate that the genital form of herpes simplex virus (type 2) is as sensitive as the oral-mouth form (type 1) to the significant therapeutic activity of ara-A.