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. 2022 Jun 24;18(6):e1010572. doi: 10.1371/journal.ppat.1010572

Fig 4. HIV-1 mediates downregulation of CD155 on infected CD4+ T cells in a Nef-dependent manner.

Fig 4

(A) Expression levels of HLA-ABC, HLA-E, CD155 and tetherin were compared between HIV-1-infected (CH077) and uninfected CD4+ T cells. HIV-1-infected cells were determined by gating on p24+ CD4dim cells and uninfected cells were defined as p24- and CD4+. Histograms show surface expression of the indicated molecules on HIV-1-infected (red), uninfected (blue) and mock infected (black) CD4+ T cells. Dot plots display surface expression of HLA-ABC, HLA-E, CD155 and tetherin on p24- and p24+ CD3+ T cells. (B) Modulation of CD155 expression on HIV-1-infected CD4+ T cells was assessed by using different HIV-1 cell line-adapted (NL4-3, JR-CSF) and primary strains (CH077, CH164, CH185, CH198, CH236, CH293). Mock-infected cells served as a control. The left graph shows CD155 expression on uninfected (blue) compared to infected (red) cells depicted as MFI. Each dot represents the result of one independent experiment. The right graph shows the median relative change (%) of CD155 expression mediated by the different HIV-1 strains, which was calculated as (MFI infected–MFI uninfected)/MFI uninfected × 100. HIV-1 strains (NL4-3, JR-CSF, CH077, CH164, CH185, CH198 and CH236) showed a significant downregulation of CD155 on infected cells (NL4-3, CH077, CH164, CH198 p = 0.016; JR-CSF, CH185, CH236 p = 0.03), calculated by performing the Wilcoxon matched-pairs signed rank test. Samples <150 cells were excluded, resulting in varying numbers of donors per condition. (C) HIV-1 wild type (wt) strains that showed the strongest CD155 downregulation (NL4-3, CH077, CH198) were compared to ΔNef mutant viruses and analyzed for their ability to downmodulate HLA-ABC and CD155. Expression levels depicted as MFI are shown for mock (black), wt virus (red) and ΔNef virus (white) infected CD4+ T cells (n = 5). The median relative change of CD155 expression is shown for wt (red) and ΔNef mutant viruses (white). Mann-Whitney test was used to calculate statistical significance of differences between the downregulation of CD155 by HIV-1 wt and ΔNef mutant viruses (p = 0.008).