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  4. The Nef protein of HIV-1 associates with rafts and primes T cells for activation
 
research article

The Nef protein of HIV-1 associates with rafts and primes T cells for activation

Wang, J K
•
Kiyokawa, E
•
Verdin, E
Show more
2000
Proceedings Of The National Academy Of Sciences Of The United States Of America (PNAS)

The Nef protein is an important virulence factor of primate lentiviruses, yet the mechanisms by which it exerts this influence are imperfectly understood. Here, using an inducible system, we demonstrate 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. Together with several proteins involved in the initiation and propagation of T cell signaling, Nef associates with membrane microdomains known as rafts. The Nef-mediated superinduction of IL-2 reflects the activation of both NFAT and NFkappaB. Accordingly, Nef also enhances HIV-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 HIV-1 replication and the facilitation of virus spread.

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Type
research article
DOI
10.1073/pnas.97.1.394
Author(s)
Wang, J K
Kiyokawa, E
Verdin, E
Trono, Didier  
Date Issued

2000

Publisher

National Academy of Sciences

Published in
Proceedings Of The National Academy Of Sciences Of The United States Of America (PNAS)
Volume

97

Issue

1

Start page

394

End page

9

Subjects

Nuclear Proteins

Editorial or Peer reviewed

NON-REVIEWED

Written at

EPFL

EPFL units
LVG  
Available on Infoscience
September 5, 2005
Use this identifier to reference this record
https://infoscience.epfl.ch/handle/20.500.14299/215866
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