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 essential for the infectivity of virions produced by non-permissive cells. The primary replicative defect of Vif particles involves either synthesis or stability of viral DNA, but the mechanism of this defect is unknown. Here, we report the results of a detailed analysis of HIV-1 DNA synthesis by isogenic Vif mutants produced by different chronically infected H9 clones, which exhibit different deg rees of impairment in their replicative capacity. We found that the degree of impairment of DNA synthesis by the mutant particles always correlated with the degree of their loss of infectivity. This impairment appears to be global, with a defect increasing along with synthesis of longer viral DNA species. We conclude that the primary replicative defect of Vif(-) virus involves the capacity of the reverse transcription complex of HIV-1 to efficiently elongate viral DNA, resulting in an inability to produce full-length viral DNA genomes.