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J. Biol. Chem., Vol. 277, Issue 8, 6137-6142, February 22, 2002

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HIV Nef Increases T Cell ERK MAP Kinase Activity^*

Jeffrey A. Schrager, Violette Der Minassian, and Jon W. Marsh^§

From the Laboratory of Molecular Biology, National Institute of Mental Health, Bethesda, Maryland 20892-4034

The human immunodeficiency regulatory protein Nef enhances viral replication and is central to viral pathogenesis. Although Nef has displayed a capacity to associate with a diverse assortment of cellular molecules and to increase T cell activity, the biochemical activity of Nef in T cells remains poorly defined. In this report we examine the bioactivity of Nef in primary CD4 T cells and, in particular, focus on the biochemical pathways known to be central to T cell activity. The extracellular signal-regulated kinase (ERK) mitogen-activated protein (MAP) kinase pathway was dramatically affected by Nef expression with increases in ERK, MEK, and Elk induction. The capacity of Nef to increase the MAP kinase pathway activity was dependent on T cell receptor stimulation. By increasing ERK MAP kinase activity, Nef is functionally associated with a kinase known to affect T cell activity, viral replication, and viral infectivity.

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