Extracellular ATP signals in an autocrine and paracrine way through purinergic receptors to modulate an array of cellular functions. In the Journal of Experimental Medicine, Perfettini and colleagues show that the HIV-1-encoded envelope glycoprotein complex (Env) can stimulate the pannexin-1-mediated release of ATP from target cells, perhaps as a result of mechanical stress on the cell membrane, which in turn favors the initial steps of HIV-1 infection. ATP activates the purinergic receptor P2Y2, which accumulates in the virological synapse and is required for depolarization of the plasma membrane. Phosphorylated Pyk2, a kinase known to participate in actin cytoskeleton reorganization, also accumulates at the virological synapse, although the link between the activation of P2Y2 and Pyk2 and membrane depolarization remains unclear. Inhibition of any of the constituents of this pathway (pannexin-1, ATP, P2Y2, Pyk2) interferes with viral entry.
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Visan, I. Early steps of HIV-1 infection. Nat Immunol 12, 931 (2011). https://doi.org/10.1038/ni.2128
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DOI: https://doi.org/10.1038/ni.2128
