Chemically selected subclones of the CEM cell line demonstrate resistance to HIV-1 infection resulting from a selective loss of NF-kappa B DNA binding proteins.
Qian, J.; Bours, Vincent; Manischewitz, J.et al.
1994 • In Journal of Immunology, 152 (8), p. 4183-91
[en] To delineate cellular genes that are required for optimal HIV-1 infection, CEM cells were subjected to treatment with the chemical mutagen ethylmethanesulfonate (EMS) and subclones were selected based on their increased resistance to HIV-1 infection and reduced syncytium formation, despite relatively normal CD4 expression (20,000 to 25,000 receptors/cell). Two subclones with this phenotype demonstrated a diminished capacity of HIV-1 long terminal repeat-chloramphenicol acetyl transferase expression either after treatment with the protein kinase C activator PMA, or through Tat-mediated transactivation. In this study, we show that the cellular levels of the NF-kappa B DNA binding proteins (but not AP1 or SP1) are markedly reduced in these cell mutants both at the mRNA and protein levels, resulting in reduced nuclear localization of p50/p65 after PMA induction or treatment with the lymphokine TNF-alpha. Transient reconstitution with a plasmid expressing p50 resulted in partial recovery of PMA-inducible LTR-chloramphenicol acetyl transferase expression. These data suggest that, at least in the CEM T cell line, a selective reduction in the NF-kappa B DNA binding proteins is sufficient to curtail HIV-1 infection.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Qian, J.
Bours, Vincent ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > GIGA-R : Génétique humaine
Manischewitz, J.
Blackburn, R.
Siebenlist, U.
Golding, H.
Language :
English
Title :
Chemically selected subclones of the CEM cell line demonstrate resistance to HIV-1 infection resulting from a selective loss of NF-kappa B DNA binding proteins.
Publication date :
1994
Journal title :
Journal of Immunology
ISSN :
0022-1767
eISSN :
1550-6606
Publisher :
American Association of Immunologists, Baltimore, United States - Maryland
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