Figure 6. HIV exploits BIRC5 for cell survival upon infection of genital T cells.

(A) F4.HSA preferentially infects Tm cells with high levels of BIRC5, and then further upregulates expression of this protein during infection. *p<0.05, **p<0.01 as assessed using the Student’s paired t test. (B) Left: Representative plots of CyTOF analysis of the frequencies of HIV-infected cells in the absence vs. presence of the BIRC5 inhibitor YM155 (200 nM). Results are gated on live, singlet Tm cells. Right: Data from 3 donors (Donors 11–13, Supplementary file 1) demonstrating significant decrease in proportion of HIV-infected cells upon YM155 treatment. (C) HIV-infected cells that persist in the presence of YM155 are more pro-apoptotic as assessed by higher expression levels of cleaved caspase-3 relative to infected cells that were never exposed to YM155. (D) Left: SLIDE analysis revealing significantly higher remodeling in the productively-infected YM155-treated cells than in the uninfected YM155-treated cells. *p<0.05, **p<0.01 as assessed using the Student’s paired t test. Right: YM155 promotes death of some infected Tm over others. t-SNE plots of uninfected (grey) and PRE (red) cells for cultures exposed or not to YM155. Highlighted in blue is a region of the t-SNE preferentially devoid of PRE cells in the YM155 sample, suggesting preferential killing of these cells upon infection. Data are representative of a total of 3 independent donors. (E) Antigens differentially expressed on HIV-susceptible cells that survive infection in the presence of YM155. PRE cells from YM155-exposed cultures were compared to those from cultures never exposed to the drug for expression levels of the indicated antigens. Left: Representative histogram plots. Right: Cumulative data from 3 donors. *p<0.05, as assessed using the Student’s paired t test. n.s.: non-significant.