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.
Extracellular ATP acts on P2Y2 purinergic receptors to facilitate HIV-1 infection / 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., et al.. - In: JOURNAL OF EXPERIMENTAL MEDICINE. - ISSN 0022-1007. - 208:9(2011), pp. 1823-1834. [10.1084/jem.20101805]
Extracellular ATP acts on P2Y2 purinergic receptors to facilitate HIV-1 infection
FIMIA, Gian Maria;
2011
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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
