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Blocking of HIV-1 infection by targeting CD4 to nonraft membrane domains

AutorReal, Gustavo del; Jiménez Baranda, Sonia; Lacalle, Rosa Ana; Mira, Emilia; Lucas, Pilar; Gómez Moutón, Concepción; Carrera, Ana C.; Martínez-Alonso, Carlos; Mañes, Santos
Palabras claveCD4
Lipid rafts
HIV-1
Lck
Infection inhibition
Fecha de publicaciónago-2002
EditorRockefeller University Press
CitaciónThe Journal of Experimental Medicine, Volume 196, Number 3, August 5, 2002, pp. 293–301
ResumenHuman immunodeficiency virus (HIV)-1 infection depends on multiple lateral interactions between the viral envelope and host cell receptors. Previous studies have suggested that these interactions are possible because HIV-1 receptors CD4, CXCR4, and CCR5 partition in cholesterol- enriched membrane raft domains. We generated CD4 partitioning mutants by substituting or deleting CD4 transmembrane and cytoplasmic domains and the CD4 ectodomain was unaltered. We report that all CD4 mutants that retain raft partitioning mediate HIV-1 entry and CD4-induced Lck activation independently of their transmembrane and cytoplasmic domains. Conversely, CD4 ectodomain targeting to a nonraft membrane fraction results in a CD4 receptor with severely diminished capacity to mediate Lck activation or HIV-1 entry, although this mutant binds gp120 as well as CD4wt. In addition, the nonraft CD4 mutant inhibits HIV-1 X4 and R5 entry in a CD4 cell line. These results not only indicate that HIV-1 exploits host membrane raft domains as cell entry sites, but also suggest new strategies for preventing HIV-1 infection.
DescripciónCopyright © by The Rockefeller University Press
URIhttp://hdl.handle.net/10261/3422
DOI10.1084/jem.20020308
ISSN0022-1007
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