THE REPLICATIVE IMPAIRMENT OF VIF(-) MUTANTS OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 CORRELATES WITH AN OVERALL DEFECT IN VIRAL-DNA SYNTHESIS

The Vif protein of human immunodeficiency virus type 1 (HIV-1) is esse ntial for the infectivity of virions produced by non-permissive cells. The primary replicative defect of Vif particles involves either synth esis or stability of viral DNA, but the mechanism of this defect is un known. Here, we report the results of a detailed analysis of HIV-1 DNA synthesis by isogenic Vif mutants produced by different chronically i nfected H9 clones, which exhibit different deg rees of impairment in t heir replicative capacity. We found that the degree of impairment of D NA synthesis by the mutant particles always correlated with the degree of their loss of infectivity. This impairment appears to be global, w ith a defect increasing along with synthesis of longer viral DNA speci es. We conclude that the primary replicative defect of Vif(-) virus in volves the capacity of the reverse transcription complex of HIV-1 to e fficiently elongate viral DNA, resulting in an inability to produce fu ll-length viral DNA genomes.