HIV Nef-mediated cellular phenotypes are differentially expressed as a function of intracellular Nef concentrations.
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.
Liu
X
X
Laboratory of Molecular Biology, National Institute of Mental Health, Bethesda, Maryland 20892-4034, USA.
Schrager
J A
JA
Lange
G D
GD
Marsh
J W
JW
D015704:CD4 Antigens / Q000235:genetics*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D002460:Cell Line; D005786:Gene Expression Regulation; D015967:Gene Expression Regulation, Viral; D015693:Gene Products, nef / Q000235:genetics / Q000378:metabolism*; D005805:Genes, MHC Class I; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D015234:HLA-A Antigens / Q000235:genetics; D006801:Humans; D019169:Jurkat Cells; D008164:Luminescent Proteins / Q000235:genetics; D008213:Lymphocyte Activation; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015302:Simian Immunodeficiency Virus / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology* / Q000821:virology*; D054311:nef Gene Products, Human Immunodeficiency Virus
D015704:CD4 Antigens; D015693:Gene Products, nef; D015234:HLA-A Antigens; D008164:Luminescent Proteins; D011993:Recombinant Fusion Proteins; D054311:nef Gene Products, Human Immunodeficiency Virus; D049452:Green Fluorescent Proteins