FIG. 3.

A model for NNRTI-mediated abrogation of HIV-1 replication. DNA primer strand and RNA template strand (stretches of black and white circles, respectively), RT (large gray oval), and NNRTI (dark gray cylinder) are shown schematically. The thick arrow reflects sequential events during HIV-1 replication in the presence of NNRTI. Once initiated, polymerization continues until NNRTI binds to RT-template-primer complex forming a PI complex. The left panel represents events for wild-type RT leading to NNRTI-sensitive phenotype; the middle and right panels represent events for RT with reduced affinity to NNRTI and RNase H-defective RT, which lead to NNRTI-resistant phenotype. The sequential events in the reverse transcription during NNRTI exposure include RNase H cleavage, dissociation of NNRTI, and either formation of a PI complex for NNRTI-susceptible phenotype or continuation of polymerization for NNRTI-resistant phenotype.