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

par Percher, Florent;Ceccaldi, Pierre Emmanuel;Van Den Broeke, Anne ;Duc-Dodon, Madeleine;Afonso, Philippe P.V.;Curis, Céline;Pérès, Eléonore;Artesi, Maria;Rosewick, Nicolas ;Jeannin, Patricia;Gessain, Antoine;Gout, Olivier;Mahieux, Renaud
Référence Nature communications, 8, 15890
Publication Publié, 2017-06

Article révisé par les pairs

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Résumé :

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.