The critical role of human transcriptional repressor CTCF mRNA up-regulation in the induction of anti-HIV-1 responses in CD4+ T cells

We have employed our CD4+ T cell model named HIV-1 resistance factor (HRF(+)) to study the inducible anti-HIV-1 responses mediated through novel soluble molecules. We found that exposure to the soluble products of HRF(+) cells activated CCCTC-binding factor (CTCF) mRNA expression in HIV-1 susceptible primary and transformed CD4+ T cells and overlapped with their acquisition of transient resistance to virus. Conversely, the interference with the expression of CTCF gene in HRF(+) cells reversed the resistant phenotype and eliminated the biological potential of their cell culture supernatant to induce “HRF-like” activity in target cells. Band-shift analysis upon the nuclear fractions from HIV-1 resistant cells showed that CTCF protein bound to HIV-1 promoter and this binding prevented the formation of NF-κB/LTR complex. This evidence suggests that CTCF is an intracellular effector of HRF activity and that the acquisition of resistance to HIV-1 in CD4+ T cells is a consequence of the prior activation of CTCF gene by the soluble entity secreted by HRF(+) cells.