The human immunodeficiency virus (HIV) Rev protein is essential for viral structural protein expression (Gag, Pol, and Env) and, hence, for viral replication. In transient transfection assays, mutant forms of Rev have been identified that inhibit wild-type Rev activity and therefore suppress viral replication. To determine whether such transdominant Rev proteins could provide long-term protection against HIV infection without affecting T cell function, T leukemia cell lines were stably transduced with a retroviral vector encoding a transdominant mutant of the Rev protein, M10. While all the M10-expressing cell lines remained infectable by HIV-1, these same cells failed to support a productive replication cycle when infected with a cloned isolate of HIV-1. In addition, two out of three M10-expressing CEM clones were also resistant to highly productive infection by a heterogeneous HIV-1 pool. Expression of M10 did not affect induction of HIV transcription mediated by the kappa B regulatory element or Tat. Importantly, constitutive expression of Rev M10 did not alter the secretion of interleukin 2 in response to mitogen stimulation of EL-4 and Jurkat cells. The inhibition of HIV infection in cells stably expressing a transdominant Rev protein, in the absence of any deleterious effect on T cell function, suggests that such a strategy could provide a therapeutic effect in the T lymphocytes of acquired immunodeficiency syndrome patients.
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October 01 1992
Stable expression of transdominant Rev protein in human T cells inhibits human immunodeficiency virus replication.
M H Malim,
M H Malim
Howard Hughes Medical Institute, Ann Arbor, Michigan.
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W W Freimuth,
W W Freimuth
Howard Hughes Medical Institute, Ann Arbor, Michigan.
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J Liu,
J Liu
Howard Hughes Medical Institute, Ann Arbor, Michigan.
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T J Boyle,
T J Boyle
Howard Hughes Medical Institute, Ann Arbor, Michigan.
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H K Lyerly,
H K Lyerly
Howard Hughes Medical Institute, Ann Arbor, Michigan.
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B R Cullen,
B R Cullen
Howard Hughes Medical Institute, Ann Arbor, Michigan.
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G J Nabel
G J Nabel
Howard Hughes Medical Institute, Ann Arbor, Michigan.
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M H Malim
Howard Hughes Medical Institute, Ann Arbor, Michigan.
W W Freimuth
Howard Hughes Medical Institute, Ann Arbor, Michigan.
J Liu
Howard Hughes Medical Institute, Ann Arbor, Michigan.
T J Boyle
Howard Hughes Medical Institute, Ann Arbor, Michigan.
H K Lyerly
Howard Hughes Medical Institute, Ann Arbor, Michigan.
B R Cullen
Howard Hughes Medical Institute, Ann Arbor, Michigan.
G J Nabel
Howard Hughes Medical Institute, Ann Arbor, Michigan.
Online ISSN: 1540-9538
Print ISSN: 0022-1007
J Exp Med (1992) 176 (4): 1197–1201.
Citation
M H Malim, W W Freimuth, J Liu, T J Boyle, H K Lyerly, B R Cullen, G J Nabel; Stable expression of transdominant Rev protein in human T cells inhibits human immunodeficiency virus replication.. J Exp Med 1 October 1992; 176 (4): 1197–1201. doi: https://doi.org/10.1084/jem.176.4.1197
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