Fig. 3: HIV infection leads to strong downregulation of the key proliferation factor MYC and decrease in cellular proliferation.
From: HIV infection reprogrammes CD4+ T cells for quiescence and entry into proviral latency
a, Several proliferative pathways and gene sets are negatively enriched at 72 hpi. For comparison, pathways changing in +vector cells during entry into and exit from the quiescence state are shown, along with those changing during the transition of +HIV 72-hpi cells to full quiescence. For this panel and in e and f, plus and minus signs at the bottom indicate positive or negative enrichment, respectively. b, Flow cytometry analysis of unpurified, minimally disturbed HIV-infected and identically treated uninfected cells after 2, 4 and 6 days of infection or mock infection indicates a reduction in proliferation markers in HIV-infected cells. The circular gate marks the position of proliferative cells prior to HIV infection or mock infection, with cells inside and outside this gate shown as purple and blue dots, respectively. c, HIV infection leads to a slowdown of cellular proliferation. Uninfected and HIV infected cells from 2 healthy donors were grown in proliferative media in the presence of IL-2 and IL-7, and cell numbers for each group were counted at indicated timepoints after infection or mock infection. In this panel and in h, values shown are the mean ± s.d. of 2 biological replicates. d, CellTrace proliferation assays confirm the slowed proliferation rate of HIV-infected cells. Peaks representing cells with decreasing CellTrace signal mark each round of cell division after the application of CellTrace Yellow stain (see Methods). e, Targets of proliferative transcription factors including MYC and E2F1 are negatively enriched 72 h after HIV infection. For comparison, changes in transcription factor activity during entry into and exit from quiescence in +vector cells are shown. f, Knockdown of MYC in CD4+ T cells results in a transcriptomic profile closely similar to the one observed 72 h after HIV infection, characterized by the negative enrichment of key proliferative pathways. g,h, Knockdown of MYC using siRNAs (siMYC) results in strong loss of expression of Ki67 and cyclins D3 and B1 compared to cells treated with a non-targeting siRNA. Both control and knockdown cells obtained from a total of 3 healthy donors (2 donors in h) were incubated in proliferative media containing high levels of IL-2. Circular gate in g marks the position of proliferative cells, with cells inside and outside the gate shown in blue and red, respectively.
