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Le Touquet – Paris-Plage, France

Gougeon M.-L.,Biotherapy and Vaccine Unit | Herbeuval J.-P.,University of Paris Descartes
Experimental Cell Research | Year: 2012

IFN-α is rapidly upregulated in response to viral infections and it is an essential player in innate immunity against viruses. pDCs are the most potent IFN-α-producing cells and serve as an essential link between innate and adaptive immunity. The fate of pDCs in the course of HIV-1 infection is still a matter of debate, and the question of the detrimental role of chronic production of IFN-α remains open. In particular, IFN-α has been shown to induce the expression of the death ligand TRAIL on pDCs, transforming them into killer pDCs that may contribute to the destruction of CD4 + T cells, the hallmark of HIV-1-induced disease. In this review, we discuss our current understanding of the protective and pathogenic roles of both IFN-α and TRAIL in HIV-1 disease. © 2012 Elsevier Inc. Source

Seror C.,French Institute of Health and Medical Research | Seror C.,Institute Gustave Roussy | Seror C.,University Paris - Sud | Melki M.-T.,Biotherapy and Vaccine Unit | And 52 more authors.
Journal of Experimental Medicine | Year: 2011

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 Envexpressing membranes and membranes containing CD4 plus appropriate chemokine coreceptors. 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. Source

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