HLA-C downregulation by HIV-1 adapts to host HLA genotype
Fig 2
HLA-C downregulation in untreated HIV-1 infection.
(A) Infectious molecular clones were assessed for ability to downregulate HLA-C for 3 individuals: CH040, 162, 058. Representative staining is shown for primary CD4+ cells infected in vitro, with HLA-C staining compared between infected and uninfected cells within a culture. (B) For the 3 individuals infectious molecular clones of both transmitted/founder viruses and those 6 months after infection were tested. HLA-C staining is shown for infected (red) and uninfected cells (black) compared to an isotype control stain (grey). (C) For ART-naïve individuals multiple cloned Vpu molecules were measured for ability to downregulate HLA-C by transfection of HeLa cells, with transfected cells in a culture identified by co-transfection of a GFP expression plasmid. (D) Staining for HLA-C is shown for Vpu clones with differential downregulation, showing transfected (red) and untransfected cells (black) compared to an isotype control (grey). (E) HLA-C downregulation is shown for 15 Vpu clones from one individual sampled at 3 timepoints over 10 years. (F-H) HLA-C downregulation observed for multiple clones from a single timepoint for 3 individuals. (I,J) HLA-C downregulation observed for dominant Vpu clones from longitudinal timepoints for 2 individuals.