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 Kanellopoulos 8 Jean-François Mouscadet 3 David Ojcius 5, 11 Mauro Piacentini 10, 12 Marie-Lise Gougeon 2 Guido Kroemer 13, 1 Jean-Luc Perfettini 1, 14, 15, 16
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.
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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, Rockefeller University Press, 2011, 208 (9), pp.1823-1834. ⟨10.1084/jem.20101805⟩. ⟨hal-02356570⟩



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