Extracellular ATP acts on P2Y2 purinergic receptors to facilitate HIV-1 infection.
| Autor: | Séror C; Institut National de la Santé et de la Recherche Médicale (INSERM) U848, F-94805 Villejuif, France., Melki MT, Subra F, Raza SQ, Bras M, Saïdi H, Nardacci R, Voisin L, Paoletti A, Law F, Martins I, Amendola A, Abdul-Sater AA, Ciccosanti F, Delelis O, Niedergang F, Thierry S, Said-Sadier N, Lamaze C, Métivier D, Estaquier J, Fimia GM, Falasca L, Casetti R, Modjtahedi N, Kanellopoulos J, Mouscadet JF, Ojcius DM, Piacentini M, Gougeon ML, Kroemer G, Perfettini JL |
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| Jazyk: | angličtina |
| Zdroj: | The Journal of experimental medicine [J Exp Med] 2011 Aug 29; Vol. 208 (9), pp. 1823-34. Date of Electronic Publication: 2011 Aug 22. |
| DOI: | 10.1084/jem.20101805 |
| Abstrakt: | 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. (© 2011 Séror et al.) |
| Databáze: | MEDLINE |
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