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-kappaB/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.
Li
Yuchang
Y
Molecular Virology Division, St. Luke's-Roosevelt Hospital Center, Columbia University Medical Center, New York, NY 10019, USA.
Li
Guanhua
G
Ivanova
Anna
A
Aaron
Sagiv
S
Simm
Malgorzata
M
D000076246:CCCTC-Binding Factor; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism / Q000821:virology*; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D016325:HIV Long Terminal Repeat; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D008264:Macrophages / Q000378:metabolism / Q000821:virology; D011506:Proteins / Q000032:analysis / Q000378:metabolism; D034622:RNA Interference; D012333:RNA, Messenger / Q000096:biosynthesis; D012097:Repressor Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
D000076246:CCCTC-Binding Factor; C000619697:CTCF protein, human; D004268:DNA-Binding Proteins; D011506:Proteins; D012333:RNA, Messenger; D012097:Repressor Proteins