Expression of the type 1 human immunodeficiency virus Nef protein in T cells prevents antigen receptor-mediated induction of interleukin 2 mRNA.

Abstract

Stable transformants of the Jurkat T-cell line have been obtained that express either of two distinct forms of the type 1 human immunodeficiency virus nef gene: the nef-1-encoded protein (Nef-1) contains alanine, glycine, and valine at positions 15, 29, and 33, respectively; the protein specified by nef-2 (Nef-2) has threonine, arginine, and alanine at the corresponding positions. When Jurkat cells or their Nef-2-expressing transformants are treated with phorbol 12-myristate 13-acetate (PMA) plus either phytohemagglutinin (PHA) or antibodies against CD3 epsilon, T-cell receptor beta chain, or CD2, there is a prompt increase in interleukin 2 (IL-2) mRNA and intracellular calcium and in the IL-2 receptor alpha chain on the cell surface. Although cells expressing Nef-1 also induce calcium mobilization and the production of IL-2 receptor alpha chain, the formation of IL-2 mRNA is blocked in response to these stimuli. Moreover, Nef-1-expressing cells transfected with a plasmid in which the IL-2 promoter is fused to the chloramphenicol acetyltransferase (CAT) gene fail to induce CAT following treatment with PMA and PHA. By contrast, the parental and Nef-2-containing cells induce CAT normally. Nef-1-expressing cells can produce IL-2 mRNA in response to a combination of PMA and ionomycin, although much less efficiently than the parental Jurkat cells or Nef-2-expressing cells. These findings, and others described herein, suggest that the virally encoded Nef protein interferes with a signal emanating from the T-cell receptor complex that induces IL-2 gene transcription.

Differential production of IL-10 by T cells and monocytes of HIV-infected individuals: association of IL-10 production with CD28-mediated immune responsiveness

“…It is also likely that HIV antigens tat, nef, gp120 or other HIV antigens may differentially regulate IL-10 in T cells and monocytes. HIV antigens tat and nef down-regulate the expression of several cellular genes including the cytokine genes [42][43][44]. The role of HIV antigens and/or cytokines in inhibiting IL-10 production by T cells at the transcriptional or post-transcriptional level remains to be determined.…”

Nef Is Physically Recruited into the Immunological Synapse and Potentiates T Cell Activation Early after TCR Engagement

“…2A and Supplementary Movie 1). 5 GFP localizing in the cytoplasm and nucleus did not migrate into the IS after T cell activation ( Fig. 2A and Supplementary Movie 1).…”

HIV Nef Inhibits T Cell Migration

“…Among the regulatory proteins is Nef, whose role in viral infection and disease progression has been controversial (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11). Among the putative functions attributed to Nef are the maintenance of high viral load (1) and immune evasion due to its down-regulation of CD4 (2) and MHC I molecules (7).…”