The NF kappa B independent cis-acting sequences in HIV-1 LTR responsive to T-cell activation.
The rate of transcription initiation directed by the long terminal repeat (LTR) of HIV-1 increases in response to mitogenic stimuli of T cells. Here we show that the response of the HIV-1 LTR may be governed by two independent sequences located 5' to the site of transcription initiation sequences that bind either NFAT-1 or NF kappa B. The rate of LTR-directed gene expression increased in response to treatment with either a phorbol ester or tumor necrosis factor alpha if either the NFAT-1 or NF kappa B binding sites were deleted, but failed to respond to these mitogenic stimuli if both sequences were absent. The HIV-1 mutant virus containing both NF kappa B and NFAT-1 deletion was able to replicate although at a much decreased growth rate, while the deletion of NFAT-1 alone increased the viral growth rate in Jurkat cells. Neither deletion of NF kappa B nor deletion of NFAT-1 decreased activation of viral replication by phorbol ester.
Lu
Y C
YC
Dana-Farber Cancer Institute, Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115.
Touzjian
N
N
Stenzel
M
M
Dorfman
T
T
Sodroski
J G
JG
Haseltine
W A
WA
D002460:Cell Line; D015870:Gene Expression; D016322:HIV Enhancer / Q000235:genetics; D016325:HIV Long Terminal Repeat / Q000235:genetics*; D015497:HIV-1 / Q000235:genetics* / Q000502:physiology; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects / Q000502:physiology*; D016328:NF-kappa B / Q000235:genetics / Q000502:physiology*; D010957:Plasmids; D013601:T-Lymphocytes / Q000502:physiology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014779:Virus Replication
D016328:NF-kappa B; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D013755:Tetradecanoylphorbol Acetate