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

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dc.creator Real, Gustavo del
dc.creator Jiménez Baranda, Sonia
dc.creator Lacalle, Rosa Ana
dc.creator Mira, Emilia
dc.creator Lucas, Pilar
dc.creator Gómez Moutón, Concepción
dc.creator Carrera, Ana C.
dc.creator Martínez-Alonso, Carlos
dc.creator Mañes, Santos
dc.date 2008-04-02T12:31:03Z
dc.date 2008-04-02T12:31:03Z
dc.date 2002-08
dc.date.accessioned 2017-01-31T01:01:26Z
dc.date.available 2017-01-31T01:01:26Z
dc.identifier The Journal of Experimental Medicine, Volume 196, Number 3, August 5, 2002, pp. 293–301
dc.identifier 0022-1007
dc.identifier http://hdl.handle.net/10261/3422
dc.identifier 10.1084/jem.20020308
dc.identifier.uri http://dspace.mediu.edu.my:8181/xmlui/handle/10261/3422
dc.description Copyright © by The Rockefeller University Press
dc.description Human 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.
dc.description Peer reviewed
dc.format 374917 bytes
dc.format application/pdf
dc.language eng
dc.publisher Rockefeller University Press
dc.rights openAccess
dc.subject CD4
dc.subject Lipid rafts
dc.subject HIV-1
dc.subject Lck
dc.subject Infection inhibition
dc.title Blocking of HIV-1 infection by targeting CD4 to nonraft membrane domains
dc.type Artículo


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