TY - JOUR
T1 - CD28 ligation in the absence of TCR promotes relA/NF-κB recruitment and trans-activation of the HIV-1LTR
AU - Annibaldi, Alessandro
AU - Sajeva, Angela
AU - Muscolini, Michela
AU - Ciccosanti, Fabiola
AU - Corazzari, Marco
AU - Piacentini, Mauro
AU - Tousto, Loretta
PY - 2008/5
Y1 - 2008/5
N2 - CD28 is one of the most important co-stimulatory receptors necessary for full T lymphocyte activation. CD28 can act as a TCR-independent signalling unit by delivering specific signals which may induce HIV transcription and replication. However, the mechanisms by which CD28 regulates HIV expression remain largely unknown. Here we show that the TCR-independent CD28 signals lead to the trans-activation of HIV-1 LTR in an NF-kB-dependent manner. In particular, we found that CD28 engagement by B7 induces the specific recruitment of ReIA/NF-kB subunit to the HIV-1 LTR promoter both in vitro and in ex vivo infected cells. The results obtained by mutating specific tyrosine residues within the CD28 cytoplasmic tail as well as by using LY294002 inhibitory drug evidenced that the recruitment and activation of the phosphatidylinositol 3-kinase/Akt signalling pathway is crucial in mediating CD28-induced HIV transcription through RelA/NF-κB.
AB - CD28 is one of the most important co-stimulatory receptors necessary for full T lymphocyte activation. CD28 can act as a TCR-independent signalling unit by delivering specific signals which may induce HIV transcription and replication. However, the mechanisms by which CD28 regulates HIV expression remain largely unknown. Here we show that the TCR-independent CD28 signals lead to the trans-activation of HIV-1 LTR in an NF-kB-dependent manner. In particular, we found that CD28 engagement by B7 induces the specific recruitment of ReIA/NF-kB subunit to the HIV-1 LTR promoter both in vitro and in ex vivo infected cells. The results obtained by mutating specific tyrosine residues within the CD28 cytoplasmic tail as well as by using LY294002 inhibitory drug evidenced that the recruitment and activation of the phosphatidylinositol 3-kinase/Akt signalling pathway is crucial in mediating CD28-induced HIV transcription through RelA/NF-κB.
KW - CD28
KW - HIV
KW - NF-κB
UR - http://www.scopus.com/inward/record.url?scp=47049108132&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=47049108132&partnerID=8YFLogxK
U2 - 10.1002/eji.200737854
DO - 10.1002/eji.200737854
M3 - Article
C2 - 18389481
AN - SCOPUS:47049108132
VL - 38
SP - 1446
EP - 1451
JO - European Journal of Immunology
JF - European Journal of Immunology
SN - 0014-2980
IS - 5
ER -