Association of human immunodeficiency virus type 1 vif with RNA and its role in reverse transcription

The vif gene of human immunodeficiency virus type 1 (HIV-1) is essential fo r viral replication, although the functional target of Vif remains elusive. HIV-1 vif mutant virions derived from nonpermissive H9 cells displayed no significant differences in the amount, ratio, or integrity of their protein composition relative to an isogenic wild-type virion. The amounts of the v irion-associated viral genomic RNA and tRNA(3)(Lys) were additionally prese nt at normal levels in vif mutant virions. We demonstrate that Vif associat es with RNA. in vitro as well as with viral genomic RNA in virus-infected c ells. A functionally conserved lentivirus Vif motif was found in the double -stranded RNA binding domain of Xenopus laevis, Xlrbpa. The natural intravi rion reverse transcriptase products were markedly reduced in vif mutant vir ions. Moreover, purified vif mutant genomic RNA-primer tRNA complexes displ ayed severe defects in the initiation of reverse transcription with recombi nant reverse transcriptase. These data point to a novel role for Vif in the regulation of efficient reverse transcription through modulation of the vi rion nucleic acid components.