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Vif is required for HIV-1 replication in natural target cells by counteracting host restriction factors, APOBEC3 (A3) proteins. We recently demonstrated that Vif expression level can be changed by naturally occurring single-nucleotide variations within SA1D2prox of the HIV-1 genome. We also found that levels for  vif / vpr  mRNAs are inversely correlated. While amino acid sequence per se is critical for functionality, Vif expression level modulated by signal sequences in its coding region is likely to be important as well. There are two splicing sites in the region involved in  vpr  expression. To reveal possible fluctuations of Vif-expression level, we examined SA1D2prox and  vif  gene by chimeric approaches using HIV-1 subtypes B and C with distinct anti-A3 activity. In this report, recombinant clones in subtype B backbone carrying chimeric sequences with respect to SA1D2prox/ vif  and those within the  vif -coding region were generated. Of these, clones containing  vif -coding sequence of subtype C, especially its 3′ region, expressed  vif /Vif at a decreased level but did at an increased level for  vpr /Vpr. Clones with reduced  vif /Vif level grew similarly or slightly better than a parental clone in weakly A3G-positive cells but more poorly in highly A3G-expressing cells. Three clones with this property were also tested for their A3-degrading activity. One of the clones appeared to have some defect in addition to the poor ability to express  vif/ Vif. Taken all together, our results show that natural variations in the SA1D2prox and  vif -coding region can change the Vif-expression level and affect the HIV-1 replication potential.

frontiers in microbiology

Expression Level of HIV-1 Vif Can Be Fluctuated by Natural Nucleotide Variations in the vif-Coding and Regulatory SA1D2prox Sequences of the Proviral Genome