Simultaneous zinc-finger nuclease editing of the HIV coreceptors ccr5 and cxcr4 protects CD4+ T cells from HIV-1 infection.
Blood
; 123(1): 61-9, 2014 Jan 02.
Article
en En
| MEDLINE
| ID: mdl-24162716
ABSTRACT
HIV-1 entry into CD4(+) T cells requires binding of the virus to CD4 followed by engagement of either the C-C chemokine receptor 5 (CCR5) or C-X-C chemokine receptor 4 (CXCR4) coreceptor. Pharmacologic blockade or genetic inactivation of either coreceptor protects cells from infection by viruses that exclusively use the targeted coreceptor. We have used zinc-finger nucleases to drive the simultaneous genetic modification of both ccr5 and cxcr4 in primary human CD4(+) T cells. These gene-modified cells proliferated normally and were resistant to both CCR5- and CXCR4-using HIV-1 in vitro. When introduced into a humanized mouse model of HIV-1 infection, these coreceptor negative cells engraft and traffic normally, and are protected from infection with CCR5- and CXCR4-using HIV-1 strains. These data suggest that simultaneous disruption of the HIV coreceptors may provide a useful approach for the long-term, drug-free treatment of established HIV-1 infections.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Linfocitos T CD4-Positivos
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Infecciones por VIH
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Dedos de Zinc
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Receptores CCR5
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Receptores CXCR4
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Endodesoxirribonucleasas
Límite:
Animals
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Female
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Humans
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Male
Idioma:
En
Revista:
Blood
Año:
2014
Tipo del documento:
Article