TY - JOUR
T1 - Extracellular ATP acts on P2Y2 purinergic receptors to facilitate HIV-1 infection
AU - Séror, Claire
AU - Melki, Marie Thérèse
AU - Subra, Frédéric
AU - Raza, Syed Qasim
AU - Bras, Marlène
AU - Saïdi, Héla
AU - Nardacci, Roberta
AU - Voisin, Laurent
AU - Paoletti, Audrey
AU - Law, Frédéric
AU - Martins, Isabelle
AU - Amendola, Alessandra
AU - Abdul-Sater, Ali A.
AU - Ciccosanti, Fabiola
AU - Delelis, Olivier
AU - Niedergang, Florence
AU - Thierry, Sylvain
AU - Said-Sadier, Najwane
AU - Lamaze, Christophe
AU - Métivier, Didier
AU - Estaquier, Jérome
AU - Fimia, Gian Maria
AU - Falasca, Laura
AU - Casetti, Rita
AU - Modjtahedi, Nazanine
AU - Kanellopoulos, Jean
AU - Mouscadet, Jean François
AU - Ojcius, David M.
AU - Piacentini, Mauro
AU - Gougeon, Marie Lise
AU - Kroemer, Guido
AU - Perfettini, Jean Luc
PY - 2011/1/1
Y1 - 2011/1/1
N2 - Extracellular adenosine triphosphate (ATP) can activate purinergic receptors of the plasma membrane and modulate multiple cellular functions. We report that ATP is released from HIV-1 target cells through pannexin-1 channels upon interaction between the HIV-1 envelope protein and specific target cell receptors. Extracellular ATP then acts on purinergic receptors, including P2Y2, to activate proline-rich tyrosine kinase 2 (Pyk2) kinase and transient plasma membrane depolarization, which in turn stimulate fusion between Envexpressing membranes and membranes containing CD4 plus appropriate chemokine coreceptors. Inhibition of any of the constituents of this cascade (pannexin-1, ATP, P2Y2, and Pyk2) impairs the replication of HIV-1 mutant viruses that are resistant to conventional antiretroviral agents. Altogether, our results reveal a novel signaling pathway involved in the early steps of HIV-1 infection that may be targeted with new therapeutic approaches.
AB - Extracellular adenosine triphosphate (ATP) can activate purinergic receptors of the plasma membrane and modulate multiple cellular functions. We report that ATP is released from HIV-1 target cells through pannexin-1 channels upon interaction between the HIV-1 envelope protein and specific target cell receptors. Extracellular ATP then acts on purinergic receptors, including P2Y2, to activate proline-rich tyrosine kinase 2 (Pyk2) kinase and transient plasma membrane depolarization, which in turn stimulate fusion between Envexpressing membranes and membranes containing CD4 plus appropriate chemokine coreceptors. Inhibition of any of the constituents of this cascade (pannexin-1, ATP, P2Y2, and Pyk2) impairs the replication of HIV-1 mutant viruses that are resistant to conventional antiretroviral agents. Altogether, our results reveal a novel signaling pathway involved in the early steps of HIV-1 infection that may be targeted with new therapeutic approaches.
UR - http://www.scopus.com/inward/record.url?scp=80054840705&partnerID=8YFLogxK
U2 - 10.1084/jem.20101805
DO - 10.1084/jem.20101805
M3 - Article
C2 - 21859844
AN - SCOPUS:80054840705
SN - 0022-1007
VL - 208
SP - 1823
EP - 1834
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 9
ER -