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

Claire Séror, Marie Thérèse Melki, Frédéric Subra, Syed Qasim Raza, Marlène Bras, Héla Saïdi, Roberta Nardacci, Laurent Voisin, Audrey Paoletti, Frédéric Law, Isabelle Martins, Alessandra Amendola, Ali A. Abdul-Sater, Fabiola Ciccosanti, Olivier Delelis, Florence Niedergang, Sylvain Thierry, Najwane Said-Sadier, Christophe Lamaze, Didier MétivierJérome Estaquier, Gian Maria Fimia, Laura Falasca, Rita Casetti, Nazanine Modjtahedi, Jean Kanellopoulos, Jean François Mouscadet, David M. Ojcius, Mauro Piacentini, Marie Lise Gougeon, Guido Kroemer, Jean Luc Perfettini

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)1823-1834
Number of pages12
JournalJournal of Experimental Medicine
Volume208
Issue number9
DOIs
Publication statusPublished - Aug 29 2011

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Medicine(all)

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