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

作者：Vieira Catarina R; Munoz Olaya Jose M; Sot Jesus; Jimenez Baranda Sonia; Izquierdo Useros Nuria; Luis Abad Jose; Apellaniz Beatriz; Delgado Rafael; Martinez Picado Javier; Alonso Alicia; Casas Josefina; Nieva Jose L; Fabrias Gemma; Manes Santos; Goni Felix M^*

来源：Chemistry & Biology, 2010, 17(7): 766-775.

DOI：10.1016/j.chembiol.2010.05.023

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 (I-d) and the liquid-ordered (I-o); the putative presence of gel domains (s(o)) is not usually taken into account. We show that in phospholipid:sphingolipid:cholesterol mixtures, in which sphingomyelin (SM) promoted fluid I-o 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.

• 出版日期2010-7-30