期刊
JOURNAL OF EXPERIMENTAL MEDICINE
卷 208, 期 9, 页码 1823-1834出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20101805
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资金
- Sidaction
- Agence Nationale des Recherches sur le Sida et sur les hepatites virales
- La Ligue Nationale contre le Cancer
- European Commission
- Istituto Superiore di Sanita [40F60]
- Associazione Italiana per la Ricerca sul Cancro Funding Source: Custom
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.
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