[en] 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.
Disciplines :
Microbiology
Author, co-author :
Percher, Florent; Institut Pasteur (Paris) > Department de Virologie
Curis, Céline; Institut Pasteur (Paris) > Department de Virologie
Peres, Eléonore; ENS de Lyon > Laboratoire de Biologie et Mode ́lisation de la Cellule
Artesi, Maria ; Université de Liège - ULiège > Unit of Animal Genomics > GIGA-Research
Rosewick, Nicolas; Université de Liège - ULiège > Unit of animal Genomics > GIGA-Research
Jeannin, Patricia; Institut Pasteur (Paris) > Department de Virologie
Gessain, Antoine; Institut Pasteur (Paris) > Department de Virologie
Gout, Olivier; Fondation Ophtalmologique Adolphe de Rothschild, Paris F-75019, France > Service de Neurologie
Mahieux, Renaud; ENS de Lyon > Equipe Oncogènese Rétrovirale
Ceccaldi, Pierre-Emmanuel; Institut Pasteur (Paris) > Department de Virologie
Van den Broeke, Anne; Université de Liège - ULiège > Unit of Animal Genomics > GIGA-Research
Duc Dodon, Madeleine; ENS de Lyon > Laboratoire de Biologie et Mode ́lisation de la Cellule
Afonso, Philippe V.; Institut Pasteur (Paris) > Department de Virologie
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