Extracellular ATP acts on P2Y2 purinergic receptors to facilitate HIV-1 infection - Archive ouverte HAL Access content directly
Journal Articles Journal of Experimental Medicine Year : 2011

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

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Laurent Voisin
  • Function : Author
  • PersonId : 991389
Isabelle Martins
Florence Niedergang
Nazanine Modjtahedi

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.

Dates and versions

hal-02356570 , version 1 (08-11-2019)

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Cite

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⟩
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