The Nef protein of HlV-1 associates with rafts and primes r cells for activation

摘要

The Nef protein is an important virulence factor of primate lenti- viruses. yet the mechanisms by which it exerts this influence are imperfectly understood. Here, using an inducible system, we dem- onstrate that Nef increases IL-2 secretion from T cells stimulated via CD3 or CD28. This effect requires the conservation of the Nef myristoylation signal and SH3-binding proline-based motif. To- gether with several proteins involved in the initiation and propa- gation of T cell signaling, Nef associates with membrane microdo- mains known as rafts. The Nef-mediated superinduction of IL-2 reflects the activation of both NFAT and NFkB. Accordingly, Nef also enhances HlV-1 transcription in response to CD3 or CD28 stimulation. Nef-induced IL-2 hyperresponsiveness is also observed in primary CD4 lymphocytes. Overall, these data suggest that Nef acts at the level of rafts to prime T cells for activation. Likely consequences of this effect are the promotion of HlV-1 replication and the facilitation of virus spread.