Fig. 2: HIV infection, entry into and exit from quiescence are accompanied by strong changes in overall gene expression patterns.
From: HIV infection reprogrammes CD4+ T cells for quiescence and entry into proviral latency
a, Dimensionality reduction study using multidimensional scaling indicates the presence of strong transcriptomic changes in early timepoints following HIV infection. b, Jensen–Shannon distance analysis of the overall transcriptomic pattern of the four polarized QUECEL ex vivo models at each step of the HIV life cycle indicates strong similarities between the quiescent and 72-hpi HIV-infected cells. c, Expression of quiescence and proliferation markers at different stages of HIV and T cell life cycle points to the induction of a quiescence-like pattern 72 h following HIV infection resembling that seen in cells maintained in quiescence-inducing media for 2 weeks (cells labelled ‘Quiescence media’). Asterisks mark MYC and KLF2, key factors in regulation of T cell activated and quiescent states, respectively. d, Western blots indicating the timecourse of changes in expression of KLF2, TOB1 and two MYC-regulated effectors CDCA7L and VEGF-A at the protein level, which corroborate the pro-quiescence transcriptomic patterns observed in c following HIV infection. Molecular weight markers are shown on the left in kilodaltons (kDa). This western blot experiment was performed twice independently with similar results. dpi, days post infection. e, Several pathways from the Hallmark gene lists of mSigDB, including MYC signalling (marked by asterisks), were significantly positively and negatively enriched during transition of vector-infected and uninfected cells from proliferating to quiescent state. Numbers in parentheses indicate the number of genes in each pathway that drive the enrichment phenotype (see Methods). f, The activity of multiple transcription factors, including MYC (marked by an asterisk), show strong changes after entry into quiescence in uninfected and +vector primary CD4+ T cells.
