Extracellular ATP acts on P2Y2 purinergic receptors to facilitate HIV-1 infection

Claire Séror (1) , Marie-Thérèse Melki (2) , Frédéric Subra (3) , Syed Qasim Raza (1) , Marlène Bras (2) , Héla Saidi (2) , Roberta Nardacci (4) , Laurent Voisin (1) , Audrey Paoletti (1) , Fredéric Law (1) , Isabelle Martins (1) , Alessandra Amendola (4) , Ali Abdul-Sater (5) , Fabiola Ciccosanti (4) , Olivier Delelis (3) , Florence Niedergang (6) , Sylvain Thierry (3) , Najwane Saïd-Sadier (5) , Christophe Lamaze (7) , Didier Métivier (1) , Jérôme Estaquier (8, 9) , Gian Maria Fimia (10) , Laura Falasca (10) , Rita Casetti (10) , Nazanine Modjtahedi (1) , Jean M. Kanellopoulos (8) , Jean-François Mouscadet (3) , David M. Ojcius (5, 11) , Mauro Piacentini (10, 12) , Marie-Lise Gougeon (2) , Guido Kroemer (13, 1) , Jean-Luc Perfettini (1, 14, 15, 16)

1 U848 - Apoptose, cancer et immunité
2 IABV - Immunité Anti-virale, Biothérapie et Vaccins
3 LBPA - Laboratoire de Biologie et de Pharmacologie Appliquée
4 National Institute for Infectious Diseases "Lazzaro Spallanzani"
5 UC Merced - University of California [Merced]
6 IC UM3 (UMR 8104 / U1016) - Institut Cochin
7 Morphogénèse et Signalisation Cellulaires
8 IBBMC - Institut de biochimie et biophysique moléculaire et cellulaire
9 Infectious Diseases Research Center [Québec]
10 INMI - Istituto Nazionale di Malattie Infettive "Lazzaro Spallanzani"
11 UPD7 - Université Paris Diderot - Paris 7
12 Università degli Studi di Roma Tor Vergata [Roma]
13 Equipe labellisée Ligue contre le cancer - CRC - Inserm U1138 - Apoptose, cancer et immunité
14 UPD5 - Université Paris Descartes - Paris 5
15 CRC (UMR_S_1138 / U1138) - Centre de Recherche des Cordeliers
16 Pôle de biologie

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 Env-expressing membranes and membranes containing CD4 plus appropriate chemokine co-receptors. 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.

Domains: Life Sciences [q-bio]

Claire Séror, Marie-Thérèse Melki, Frédéric Subra, Syed Qasim Raza, Marlène Bras, et al.. Extracellular ATP acts on P2Y2 purinergic receptors to facilitate HIV-1 infection. Journal of Experimental Medicine, 2011, 208 (9), pp.1823-1834. ⟨10.1084/jem.20101805⟩. ⟨hal-02356570⟩