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Science 16 September 1988:
Vol. 241. no. 4872, pp. 1481 - 1485
DOI: 10.1126/science.3262235
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Articles

Science, Vol 241, Issue 4872, 1481-1485
Copyright © 1988 by American Association for the Advancement of Science

articles

Nef protein of HIV-1 is a transcriptional repressor of HIV-1 LTR

N Ahmad and S Venkatesan

Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892.

In studies of the genetics of human immunodeficiency virus type 1 (HIV-1), the product of the nef gene, formerly known as F, 3'-orf, or B-ORF, was a negative regulator of HIV-1 replication. Proviruses with mutations in the nef gene replicated better than their standard counterparts during transient expression, and the mutant virus maintained its enhanced replication even after serial passages in T lymphocytes. The nef protein trans-suppressed, in a dose-dependent manner, the replication of wild-type and nef mutant proviruses and the expression of reporter genes linked to the HIV-1 long terminal repeat (LTR). The repression induced by the nef protein was mediated by inhibition of transcription from the HIV-1 LTR, which contains a far upstream cis element (previously recognized to be a negative regulatory element) between 340 and 156 nucleotides upstream of the RNA initiation site.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
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Heat Shock Protein 40 Is Necessary for Human Immunodeficiency Virus-1 Nef-mediated Enhancement of Viral Gene Expression and Replication.
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Hidden messages in the nef gene of human immunodeficiency virus type 1 suggest a novel RNA secondary structure.
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Disassembly of Human Immunodeficiency Virus Type 1 Cores In Vitro Reveals Association of Nef with the Subviral Ribonucleoprotein Complex.
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IFN-{alpha} Secretion by Type 2 Predendritic Cells Up-Regulates MHC Class I in the HIV-1-Infected Thymus.
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Positive and Negative Aspects of the Human Immunodeficiency Virus Protease: Development of Inhibitors versus Its Role in AIDS Pathogenesis.
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Association of Nef with the Human Immunodeficiency Virus Type 1 Core.
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J. Virol. 73, 8824-8830
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The Proteolytic Cleavage of Human Immunodeficiency Virus Type 1 Nef Does Not Correlate with Its Ability To Stimulate Virion Infectivity.
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J. Virol. 72, 3178-3184
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Vaccine effect using a live attenuated nef-deficient simian immunodeficiency virus of African green monkeys in the absence of detectable vaccine virus replication in vivo.
B. Beer, M. Baier, J. zur Megede, S. Norley, and R. Kurth (1997)
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Physical and Functional Interaction of Nef with Lck.
Y. Collette, H. Dutartre, A. Benziane, F. Ramos-Morales, R. Benarous, M. Harris, and D. Olive (1996)
J. Biol. Chem. 271, 6333-6341
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A Conserved Domain and Membrane Targeting of Nef from HIV and SIV Are Required for Association with a Cellular Serine Kinase Activity.
E. T. Sawai, A. S. Baur, B. M. Peterlin, J. A. Levy, and C. Cheng-Mayer (1995)
J. Biol. Chem. 270, 15307-15314
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Pathogenicity of live, attenuated SIV after mucosal infection of neonatal macaques.
T. Baba, Y. Jeong, D Pennick, R Bronson, M. Greene, and R. Ruprecht (1995)
Science 267, 1820-1825
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Antiretroviral Therapy in AIDS.
S. Broder, H. Mitsuya, R. Yarchoan, and G. N. Pavlakis (1990)
Ann Intern Med 113, 604-618
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Differential effects of nef on HIV replication: implications for viral pathogenesis in the host.
C Cheng-Mayer, P Iannello, K Shaw, P. Luciw, and J. Levy (1989)
Science 246, 1629-1632
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Human Immunodeficiency Viruses and the Pathogenesis of AIDS.
J. A. Levy (1989)
JAMA 261, 2997-3006
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