Human immunodeficiency virus type 1 Nef protein inhibits NF-kappa B induction in human T cells.
Human immunodeficiency virus type 1 (HIV-1) can establish a persistent and latent infection in CD4+ T lymphocytes (W. C. Greene, N. Engl. J. Med. 324:308-317, 1991; S. M. Schnittman, M. C. Psallidopoulos, H. C. Lane, L. Thompson, M. Baseler, F. Massari, C. H. Fox, N. P. Salzman, and A. S. Fauci, Science 245:305-308, 1989). Production of HIV-1 from latently infected cells requires host cell activation by T-cell mitogens (T. Folks, D. M. Powell, M. M. Lightfoote, S. Benn, M. A. Martin, and A. S. Fauci, Science 231:600-602, 1986; D. Zagury, J. Bernard, R. Leonard, R. Cheynier, M. Feldman, P. S. Sarin, and R. C. Gallo, Science 231:850-853, 1986). This activation is mediated by the host transcription factor NF-kappa B [G. Nabel and D. Baltimore, Nature (London) 326:711-717, 1987]. We report here that the HIV-1-encoded Nef protein inhibits the induction of NF-kappa B DNA-binding activity by T-cell mitogens. However, Nef does not affect the DNA-binding activity of other transcription factors implicated in HIV-1 regulation, including SP-1, USF, URS, and NF-AT. Additionally, Nef inhibits the induction of HIV-1- and interleukin 2-directed gene expression, and the effect on HIV-1 transcription depends on an intact NF-kappa B-binding site. These results indicate that defective recruitment of NF-kappa B may underlie Nef's negative transcriptional effects on the HIV-1 and interleukin 2 promoters. Further evidence suggests that Nef inhibits NF-kappa B induction by interfering with a signal derived from the T-cell receptor complex.
Niederman
T M
TM
Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110.
Garcia
J V
JV
Hastings
W R
WR
Luria
S
S
Ratner
L
L
D001483:Base Sequence; D015153:Blotting, Western; D002460:Cell Line; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics / Q000378:metabolism; D015693:Gene Products, nef / Q000378:metabolism*; D015497:HIV-1 / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000096:biosynthesis*; D009841:Oligonucleotides; D011233:Precipitin Tests; D013601:T-Lymphocytes / Q000378:metabolism* / Q000382:microbiology; D054311:nef Gene Products, Human Immunodeficiency Virus
D015693:Gene Products, nef; D016328:NF-kappa B; D009841:Oligonucleotides; D054311:nef Gene Products, Human Immunodeficiency Virus; D015500:Chloramphenicol O-Acetyltransferase