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J Biol Chem. 2001 Aug 31;276(35):32763-70. Epub 2001 Jul 3.

HIV Nef-mediated cellular phenotypes are differentially expressed as a function of intracellular Nef concentrations.

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  • 1Laboratory of Molecular Biology, National Institute of Mental Health, Bethesda, Maryland 20892-4034, USA.


Nef is a regulatory protein encoded by the genome of both human and simian immunodeficiency virus. Its expression in T cells leads to CD4 and major histocompatibility complex class I modulation and either enhancement or suppression of T cell activation. How this viral protein achieves multiple and at times opposing activities has been unclear. Through direct measurements of Nef and the Nef-GFP fusion protein, we find that these events are mediated by different Nef concentrations. Relative to the intracellular concentration that down-modulates surface CD4, an order of magnitude increase in Nef-GFP expression is required for a comparable modulation of major histocompatibility complex class I, and a further 3-fold increase is necessary to suppress T cell activation.

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