Mechanism of Enzyme Inhibition Mediated by Anti-Reverse Transcriptase Antibodies from HIV Type 1-Infected Individuals

We have examined the mechanisms of reverse transcriptase (RT) inhibition mediated by anti-RT antibodies, isolated by affinity chromatography, from four HIV-1-positive individuals. In kinetics assays, anti-RT immunoglobulin (Ig) obtained from three of the sera mediated a noncompetitive type of inhibition against template primer; two of these three also mediated noncompetitive inhibition with respect to deoxyribonucleoside triphosphate. Such inhibition did not require that the Ig be preincubated with RT prior to the addition of reaction components. In contrast, a more complicated pattern of inhibition was exhibited by anti-RT Ig from the fourth serum. Preincubation of this Ig with enzyme markedly enhanced the inhibition. The results demonstrate that the specificities of RT-inhibiting antibodies vary among HIV-1 -infected individuals, but that one prevalent mechanism of inhibition involves interactions with epitopes outside of the enzyme active site.