Extracellular ATP acts on P2Y2 purinergic receptors to facilitate HIV-1 infectionJournal of Experimental Medicine
ORCiDDavid M. Ojcius: 0000-0003-1461-4495
AbstractExtracellular 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.
Citation InformationClaire Séror, Marie-Therese Melki, Frederic Subra, Syed Qasim Raza, et al.. "Extracellular ATP acts on P2Y2 purinergic receptors to facilitate HIV-1 infection" Journal of Experimental Medicine Vol. 208 Iss. 9 (2011) p. 1823 - 1834 ISSN: 0022-1007
Available at: http://works.bepress.com/david-ojcius/100/