TREATMENT OF VISNA VIRUS-INFECTION IN LAMBS WITH THE ACYCLIC NUCLEOSIDE PHOSPHONATE ANALOG 9-(2-PHOSPHONYLMETHOXYETHYL)ADENINE (PMEA)

Nucleoside and nucleotide analogues, which are inhibitors of human imm unodeficiency virus reverse transcriptase, are highly active inhibitor s of visna virus replication in cell cultures. One such analogue, the acyclic nucleoside phosphonate PMEA, has also been found to have a pro phylactic effect on visna virus infection in lambs. In the present stu dy, lambs were injected subcutaneously with 10 mg/kg PMEA three times a week starting 4 weeks after inoculation with visna virus, when brain infection had been established. After 3 weeks of treatment there was a reduction in the amount of virus isolated from blood cells of PMEA-t reated lambs compared to controls and during the remaining 7 months of drug treatment there was significantly less virus isolated from the b lood cells of treated lambs than of controls. Antibody response agains t visna virus was also slower in the treated than in the untreated con trol group. On the other hand, there was no difference in the amount o f virus isolated from various organs of the two groups and the severit y of CNS lesions in sheep treated with PMEA for 8 months was comparabl e to that found in untreated controls, even though PMEA reached concen trations in the cerebrospinal fluid which were well in excess of the E C50 value of the drug for visna virus.