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.

Autore Pugliese

• Fimia Gian Maria

Tutti gli autori

• Séror C. , Melki M.T. , Subra F. , Raza S.Q. , Bras M. , Saïdi H. , Nardacci R. , Voisin L. , Paoletti A. , Law F. Martins I. , Amendola A. , Abdul-Sater A.A. , Ciccosanti F. , Delelis O. , Niedergang F. , Thierry S. , Said-Sadier N. , Lamaze C. , Métivier D. , Estaquier J. , Fimia G.M. , Falasca L. , Casetti R. , Modjtahedi N. , Kanellopoulos J. , Mouscadet J.F. , Ojcius D.M. , Piacentini M. , Gougeon M.L. , Kroemer G. , Perfettini J.L.

Titolo volume/Rivista

THE JOURNAL OF EXPERIMENTAL MEDICINE

Anno di pubblicazione

2011

ISSN

1540-9538

ISBN

Non Disponibile

Numero di citazioni Wos

69

Ultimo Aggiornamento Citazioni

25/04/2018

Numero di citazioni Scopus

76

Ultimo Aggiornamento Citazioni

26/04/2018

Settori ERC

Non Disponibile

Codici ASJC

Non Disponibile