PMID- 10618429
OWN - NLM
STAT- MEDLINE
DCOM- 20000210
LR  - 20190501
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 97
IP  - 1
DP  - 2000 Jan 4
TI  - The Nef protein of HIV-1 associates with rafts and primes T cells for activation.
PG  - 394-9
AB  - 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.
FAU - Wang, J K
AU  - Wang JK
AD  - Department of Genetics and Microbiology, University of Geneva, CH-1211 Geneva,
      Switzerland.
FAU - Kiyokawa, E
AU  - Kiyokawa E
FAU - Verdin, E
AU  - Verdin E
FAU - Trono, D
AU  - Trono D
LA  - eng
GR  - R37 AI 34306/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Antigens, CD)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Gene Products, nef)
RN  - 0 (Glycolipids)
RN  - 0 (Interleukin-2)
RN  - 0 (NF-kappa B)
RN  - 0 (NFATC Transcription Factors)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Transcription Factors)
RN  - 0 (nef Gene Products, Human Immunodeficiency Virus)
RN  - 0I3V7S25AW (Myristic Acid)
SB  - IM
SB  - X
MH  - Antigens, CD/pharmacology
MH  - CD4-Positive T-Lymphocytes/*metabolism
MH  - DNA-Binding Proteins/metabolism
MH  - Gene Expression Regulation, Viral/immunology
MH  - Gene Products, nef/*pharmacology
MH  - Genes, Reporter
MH  - Glycolipids/metabolism
MH  - HIV Long Terminal Repeat/genetics
MH  - HIV-1/genetics/*metabolism
MH  - Humans
MH  - Interleukin-2/genetics/metabolism
MH  - Jurkat Cells
MH  - Lymphocyte Activation/*immunology
MH  - Myristic Acid/metabolism
MH  - NF-kappa B/metabolism
MH  - NFATC Transcription Factors
MH  - *Nuclear Proteins
MH  - Promoter Regions, Genetic
MH  - Signal Transduction
MH  - Transcription Factors/metabolism
MH  - Virus Replication
MH  - nef Gene Products, Human Immunodeficiency Virus
PMC - PMC26674
EDAT- 2000/01/05 00:00
MHDA- 2000/01/05 00:01
CRDT- 2000/01/05 00:00
PHST- 2000/01/05 00:00 [pubmed]
PHST- 2000/01/05 00:01 [medline]
PHST- 2000/01/05 00:00 [entrez]
AID - 10.1073/pnas.97.1.394 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2000 Jan 4;97(1):394-9. doi: 10.1073/pnas.97.1.394.