Exposure of human astrocytes to leukotriene C sub(4) promotes a CX3CL1/fractalkine-mediated transmigration of HIV-1-infected CD4 super(+) T cells across an in vitro blood-brain barrier model

• Published in: Virology (New York, N.Y.) Vol. 454-455; pp. 128 - 138
• Main Authors: Bertin, Jonathan, Jalaguier, Pascal, Barat, Corinne, Roy, Marc-Andre, Tremblay, Michel J
• Format: Journal Article
• Language: English
• Published: 01-04-2014
• Subjects: Human immunodeficiency virus 1
• ISSN: 0042-6822
• DOI: 10.1016/j.virol.2014.02.007

Eicosanoids, including cysteinylleukotrienes (cysLTs), are found in the central nervous system (CNS) of individuals infected with HIV-1. Few studies have addressed the contribution of cysLTs in HIV-1-associated CNS disorders. We demonstrate that conditioned medium from human astrocytes treated with leukotriene C sub(4) (LTC sub(4)) increases the transmigration of HIV-1-infected CD4 super(+) T cells across an in vitro blood-brain barrier (BBB) model using cultured brain endothelial cells. Additional studies indicate that the higher cell migration is linked with secretion by astrocytes of CX3CL1/fractalkine, a chemokine that has chemoattractant activity for CD4 super(+) T cells. Moreover, we report that the enhanced cell migration across BBB leads to a more important CD4 super(+) T cell-mediated HIV-1 transfer toward macrophages. Altogether data presented in the present study reveal the important role that LTC sub(4), a metabolite of arachidonic acid, may play in the HIV-1-induced neuroinvasion, neuropathogenesis and disease progression.