Phosphonoformate inhibition of visna virus replication

Abstract

Phosphonoformate (PFA) inhibits multiplication of visna virus in sheep choroid plexus cells; a 50% reduction of virus yield was obtained by 20-80 .mu.M PFA. Morphological changes, such as syncytial formation and cell degeneration, could be reversibly prevented by PFA. Cell growth was not significantly affected at 500 .mu.M PFA, although prolonged treatment with 2 mM PFA did arrest cell growth. Cell-free reverse transcriptase activity primed with various synthetic template-primers was inhibited about 90% in the presence of 100 .mu.M PFA. The results from kinetic experiments suggested that reverse transcriptase was utilized early but not late in the infection cycle. A structurally related substance, phosphonoacetate, did not inhibit visna virus multiplication and had no inhibitory effect on reverse transcriptase activity at a concentration of 500 .mu.M.