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Extracellular ATP acts on P2Y2 purinergic receptors to facilitate HIV-1 infection
Journal of Experimental Medicine
  • Claire Séror
  • Marie-Therese Melki
  • Frederic Subra
  • Syed Qasim Raza
  • Marlene Bras
  • Hela Saïdi
  • Roberta Nardacci
  • Laurent Voisin
  • Audrey Paoletti
  • Frederic Law
  • Isabelle Martins
  • Alessandra Amendola
  • Ali A. Abdul-Sater
  • Fabiola Ciccosanti
  • Olivier Delelis
  • Florence Niedergang
  • Sylvain Thierry
  • Najwane Said-Sadier
  • Christophe Lamaze
  • Didier Métivier
  • Jerome Estaquier
  • Gian Maria Fimia
  • Laura Falasca
  • Rita Casetti
  • Nazanine Modjtahedi
  • Jean M. Kanellopoulos
  • Jean-Francois Mouscadet
  • David M. Ojcius, University of the Pacific
  • Mauro Piacentini
  • Marie-Lise Gougeon
  • Guido Kroemer
  • Jean-Luc Perfetini
ORCiD
David M. Ojcius: 0000-0003-1461-4495
Document Type
Article
DOI
10.1084/jem.20101805
Publication Date
8-1-2011
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 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.
Citation Information
Claire Séror, Marie-Therese Melki, Frederic Subra, Syed Qasim Raza, et al.. "Extracellular ATP acts on P2Y2 purinergic receptors to facilitate HIV-1 infection" Journal of Experimental Medicine Vol. 208 Iss. 9 (2011) p. 1823 - 1834 ISSN: 0022-1007
Available at: http://works.bepress.com/david-ojcius/100/