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HTLV-1-induced leukotriene B4 secretion by T cells promotes T cell recruitment and virus propagation.

Abstract : The human T-lymphotropic virus type 1 (HTLV-1) is efficiently transmitted through cellular contacts. While the molecular mechanisms of viral cell-to-cell propagation have been extensively studied in vitro, those facilitating the encounter between infected and target cells remain unknown. In this study, we demonstrate that HTLV-1-infected CD4 T cells secrete a potent chemoattractant, leukotriene B4 (LTB4). LTB4 secretion is dependent on Tax-induced transactivation of the pla2g4c gene, which encodes the cytosolic phospholipase A2 gamma. Inhibition of LTB4 secretion or LTB4 receptor knockdown on target cells reduces T-cell recruitment, cellular contact formation and virus propagation in vitro. Finally, blocking the synthesis of LTB4 in a humanized mouse model of HTLV-1 infection significantly reduces proviral load. This results from a decrease in the number of infected clones while their expansion is not impaired. This study shows the critical role of LTB4 secretion in HTLV-1 transmission both in vitro and in vivo.
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Contributor : Philippe Afonso Connect in order to contact the contributor
Submitted on : Thursday, June 22, 2017 - 4:05:02 PM
Last modification on : Wednesday, November 9, 2022 - 1:42:09 PM
Long-term archiving on: : Wednesday, January 10, 2018 - 4:08:33 PM


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Florent Percher, Céline Curis, Eléonore Pérès, Maria Artesi, Nicolas Rosewick, et al.. HTLV-1-induced leukotriene B4 secretion by T cells promotes T cell recruitment and virus propagation.. Nature Communications, 2017, 8, pp.15890. ⟨10.1038/ncomms15890⟩. ⟨pasteur-01545491⟩



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