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

Florent Percher, Céline Curis, Eléonore Pérès, Maria Artesi, Nicolas Rosewick, Patricia Jeannin, Antoine Gessain, Olivier Gout, Renaud Mahieux, Pierre-Emmanuel Ceccaldi, Anne Van den Broeke, Madeleine Duc Dodon and Philippe V. Afonso ()
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Florent Percher: Unité d'Epidémiologie et Physiopathologie des Virus Oncogènes, Institut Pasteur
Céline Curis: Unité d'Epidémiologie et Physiopathologie des Virus Oncogènes, Institut Pasteur
Eléonore Pérès: Laboratoire de Biologie et Modélisation de la Cellule, ENS de Lyon, INSERM U1210 CNRS-UCBL UMR 5239
Maria Artesi: Unit of Animal Genomics, Groupe Interdisciplinaire Génoprotéomique Appliquée (GIGA), Université de Liège
Nicolas Rosewick: Unit of Animal Genomics, Groupe Interdisciplinaire Génoprotéomique Appliquée (GIGA), Université de Liège
Patricia Jeannin: Unité d'Epidémiologie et Physiopathologie des Virus Oncogènes, Institut Pasteur
Antoine Gessain: Unité d'Epidémiologie et Physiopathologie des Virus Oncogènes, Institut Pasteur
Olivier Gout: Service de Neurologie, Fondation Ophtalmologique Adolphe de Rothschild
Renaud Mahieux: Equipe Oncogenèse Rétrovirale, ENS de Lyon, and Equipe Labélisée Ligue Nationale Contre le Cancer, Centre International de Recherche en Infectiologie
Pierre-Emmanuel Ceccaldi: Unité d'Epidémiologie et Physiopathologie des Virus Oncogènes, Institut Pasteur
Anne Van den Broeke: Unit of Animal Genomics, Groupe Interdisciplinaire Génoprotéomique Appliquée (GIGA), Université de Liège
Madeleine Duc Dodon: Laboratoire de Biologie et Modélisation de la Cellule, ENS de Lyon, INSERM U1210 CNRS-UCBL UMR 5239
Philippe V. Afonso: Unité d'Epidémiologie et Physiopathologie des Virus Oncogènes, Institut Pasteur

Nature Communications, 2017, vol. 8, issue 1, 1-10

Abstract: 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.

Date: 2017
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DOI: 10.1038/ncomms15890

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