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Closed Access item Dihydrosphingomyelin Impairs HIV-1 Infection by Rigidifying Liquid-Ordered Membrane Domains

Authors:Vieira, Catarina R.
Munoz-Olaya, Jose M.
Sot, Jesús
Jiménez-Baranda, Sonia
Izquierdo-Useros, Nuria
Abad, José Luis
Apellániz, Beatriz
Delgado, Rafael
Martínez-Picado, Javier
Alonso, Alicia
Casas, Josefina
Nieva, José L.
Fabriàs, Gemma
Mañes, Santos
Goñi, Félix M.
Issue Date:2010
Citation:Chemistry and Biology - Cambridge
Abstract:The lateral organization of lipids in cell membranes is thought to regulate numerous cell processes. Most studies focus on the coexistence of two fluid phases, the liquid crystalline (ld) and the liquid-ordered (lo); the putative presence of gel domains (so) is not usually taken into account. We show that in phospholipid:sphingolipid:cholesterol mixtures, in which sphingomyelin (SM) promoted fluid lo domains, dihydrosphingomyelin (DHSM) tended to form rigid domains. Genetic and pharmacological blockade of the dihydroceramide desaturase (Des1), which replaced SM with DHSM in cultured cells, inhibited cell infection by replication-competent and -deficient HIV-1. Increased DHSM levels gave rise to more rigid membranes, resistant to the insertion of the gp41 fusion peptide, thus inhibiting viral-cell membrane fusion. These results clarify the function of dihydrosphingolipids in biological membranes and identify Des1 as a potential target in HIV-1 infection.
Publisher version (URL):http://dx.doi.org/10.1016/j.chembiol.2010.05.023
E-ISSNmetadata.dc.identifier.doi = DOI:1879-1301
Appears in Collections:(IQAC) Artículos

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