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PMID: 1527859 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

Human immunodeficiency virus type 1 Nef protein inhibits NF-kappa B induction in human T cells.

Journal of virology ·Vol. 66 ·No. 10 ·1992-10-00 ·Pages 6213-9

Niederman TM, Garcia JV, Hastings WR, Luria S, Ratner L

Abstract

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.

MeSH Terms
Base Sequence Blotting, Western Cell Line Chloramphenicol O-Acetyltransferase/genetics,metabolism Gene Products, nef/metabolism HIV-1/metabolism Humans Molecular Sequence Data NF-kappa B/biosynthesis Oligonucleotides Precipitin Tests T-Lymphocytes/metabolism,microbiology nef Gene Products, Human Immunodeficiency Virus
Chemicals
Gene Products, nef NF-kappa B Oligonucleotides nef Gene Products, Human Immunodeficiency Virus Chloramphenicol O-Acetyltransferase
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Niederman T M
Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110.
Garcia J V
Hastings W R
Luria S
Ratner L
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Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/JVI.66.10.6213-6219.1992
Published
1992-10-00
Pages
6213-9
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC283675
Subset
IM
Grants
NIAID NIH HHS · AI24745 · United States
NHLBI NIH HHS · HL-07088-17 · United States
External Links
PubMed source DOI: 10.1128/JVI.66.10.6213-6219.1992 PMC Full Text View journal details
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