title: Extracellular ATP acts on P2Y2 purinergic receptors to facilitate HIV-1 infection.
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.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM) U848, F-94805 Villejuif, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Séror
authors.forename: Marie-Thérèse
authors.initials: MT
authors.lastname: Melki
authors.forename: Frédéric
authors.initials: F
authors.lastname: Subra
authors.forename: Syed Qasim
authors.initials: SQ
authors.lastname: Raza
authors.forename: Marlène
authors.initials: M
authors.lastname: Bras
authors.forename: Héla
authors.initials: H
authors.lastname: Saïdi
authors.forename: Roberta
authors.initials: R
authors.lastname: Nardacci
authors.forename: Laurent
authors.initials: L
authors.lastname: Voisin
authors.forename: Audrey
authors.initials: A
authors.lastname: Paoletti
authors.forename: Frédéric
authors.initials: F
authors.lastname: Law
authors.forename: Isabelle
authors.initials: I
authors.lastname: Martins
authors.forename: Alessandra
authors.initials: A
authors.lastname: Amendola
authors.forename: Ali A
authors.initials: AA
authors.lastname: Abdul-Sater
authors.forename: Fabiola
authors.initials: F
authors.lastname: Ciccosanti
authors.forename: Olivier
authors.initials: O
authors.lastname: Delelis
authors.forename: Florence
authors.initials: F
authors.lastname: Niedergang
authors.forename: Sylvain
authors.initials: S
authors.lastname: Thierry
authors.forename: Najwane
authors.initials: N
authors.lastname: Said-Sadier
authors.forename: Christophe
authors.initials: C
authors.lastname: Lamaze
authors.forename: Didier
authors.initials: D
authors.lastname: Métivier
authors.forename: Jérome
authors.initials: J
authors.lastname: Estaquier
authors.forename: Gian Maria
authors.initials: GM
authors.lastname: Fimia
authors.forename: Laura
authors.initials: L
authors.lastname: Falasca
authors.forename: Rita
authors.initials: R
authors.lastname: Casetti
authors.forename: Nazanine
authors.initials: N
authors.lastname: Modjtahedi
authors.forename: Jean
authors.initials: J
authors.lastname: Kanellopoulos
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Mouscadet
authors.forename: David M
authors.initials: DM
authors.lastname: Ojcius
authors.forename: Mauro
authors.initials: M
authors.lastname: Piacentini
authors.forename: Marie-Lise
authors.initials: ML
authors.lastname: Gougeon
authors.forename: Guido
authors.initials: G
authors.lastname: Kroemer
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Perfettini
mesh_terms: D000255:Adenosine Triphosphate / Q000235:genetics / Q000378:metabolism*; D000328:Adult; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods; D002462:Cell Membrane / Q000235:genetics / Q000378:metabolism*; D017630:Connexins / Q000235:genetics / Q000378:metabolism; D024882:Drug Resistance, Viral / Q000187:drug effects / Q000235:genetics; D004789:Enzyme Activation / Q000187:drug effects / Q000235:genetics; D051418:Focal Adhesion Kinase 2 / Q000235:genetics / Q000378:metabolism; D015658:HIV Infections / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D008297:Male; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D058473:Receptors, Purinergic P2Y2 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014779:Virus Replication / Q000187:drug effects / Q000235:genetics
chemical_list: D017630:Connexins; D009419:Nerve Tissue Proteins; C492764:PANX1 protein, human; D058473:Receptors, Purinergic P2Y2; D000255:Adenosine Triphosphate; D051418:Focal Adhesion Kinase 2