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