Dihydrosphingomyelin Impairs HIV-1 Infection by Rigidifying Liquid-Ordered Membrane Domains
Por:
Vieira, CR, Munoz-Olaya, JM, Sot, J, Jimenez-Baranda, S, Izquierdo-Useros, N, Abad, JL, Apellaniz, B, Delgado, R, Martinez-Picado, J, Alonso, A, Casas, J, Nieva, JL, Fabrias, G, Manes, S and Goni, FM
Publicada:
30 jul 2010
Resumen:
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.
Filiaciones:
Vieira, CR:
CSIC, Ctr Nacl Biotecnol, Dept Immunol & Oncol, E-28049 Madrid, Spain
Munoz-Olaya, JM:
CSIC, Inst Adv Chem Catalonia IQAC, Dept Biomed Chem, ES-08034 Barcelona, Spain
Sot, J:
Univ Basque Country, CSIC, Ctr Mixto, Unidad Biofis,EHU, E-48080 Bilbao, Spain
Univ Basque Country, Dept Bioquim, E-48080 Bilbao, Spain
Jimenez-Baranda, S:
CSIC, Ctr Nacl Biotecnol, Dept Immunol & Oncol, E-28049 Madrid, Spain
:
Hosp Badalona Germans Trias & Pujol, irsiCaixa Fdn, E-08916 Badalona, Spain
Abad, JL:
CSIC, Inst Adv Chem Catalonia IQAC, Dept Biomed Chem, ES-08034 Barcelona, Spain
Apellaniz, B:
Univ Basque Country, CSIC, Ctr Mixto, Unidad Biofis,EHU, E-48080 Bilbao, Spain
Univ Basque Country, Dept Bioquim, E-48080 Bilbao, Spain
Delgado, R:
Hosp Univ 12 Octubre, E-28049 Madrid, Spain
:
Hosp Badalona Germans Trias & Pujol, irsiCaixa Fdn, E-08916 Badalona, Spain
ICREA, Barcelona, Spain
Alonso, A:
Univ Basque Country, CSIC, Ctr Mixto, Unidad Biofis,EHU, E-48080 Bilbao, Spain
Univ Basque Country, Dept Bioquim, E-48080 Bilbao, Spain
Casas, J:
CSIC, Inst Adv Chem Catalonia IQAC, Dept Biomed Chem, ES-08034 Barcelona, Spain
Nieva, JL:
Univ Basque Country, CSIC, Ctr Mixto, Unidad Biofis,EHU, E-48080 Bilbao, Spain
Univ Basque Country, Dept Bioquim, E-48080 Bilbao, Spain
Fabrias, G:
CSIC, Inst Adv Chem Catalonia IQAC, Dept Biomed Chem, ES-08034 Barcelona, Spain
Manes, S:
CSIC, Ctr Nacl Biotecnol, Dept Immunol & Oncol, E-28049 Madrid, Spain
Goni, FM:
Univ Basque Country, CSIC, Ctr Mixto, Unidad Biofis,EHU, E-48080 Bilbao, Spain
Univ Basque Country, Dept Bioquim, E-48080 Bilbao, Spain
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