HIV-1 Vpu sequencing of PBMC and plasma samples from untreated HIV-1 positive individuals

Given the remarkable diversity of HLA-C molecules and its corresponding NK cell receptors KIR2DL1/2/3 (KIR2DL), we hypothesized that differential binding affinities across KIR2DL and HLA-C allotypes impact KIR2DL+ NK cell induced immune pressure and therefore contribute to Vpu-associated viral escape. Therefore, amplicon-sequencing of HIV-1 Vpu of genomic DNA from PBMCs and viral RNA from plasma samples from untreated HIV-1 positive individuals was performed to investigate Vpu sequence polymorphisms. The study provides evidence that KIR/HLA binding affinities serve as a contributing factor for HIV-1-mediated changes in the KIR2DL repertoire and the preferential selection of amino acid residues in Vpu that are linked to HLA-C downmodulation.