Highly significant antiviral activity of HIV-1 LTR-specific tre-recombinase in humanized mice.
PLoS Pathog
; 9(9): e1003587, 2013.
Article
en En
| MEDLINE
| ID: mdl-24086129
Stable integration of HIV proviral DNA into host cell chromosomes, a hallmark and essential feature of the retroviral life cycle, establishes the infection permanently. Current antiretroviral combination drug therapy cannot cure HIV infection. However, expressing an engineered HIV-1 long terminal repeat (LTR) site-specific recombinase (Tre), shown to excise integrated proviral DNA in vitro, may provide a novel and highly promising antiviral strategy. We report here the conditional expression of Tre-recombinase from an advanced lentiviral self-inactivation (SIN) vector in HIV-infected cells. We demonstrate faithful transgene expression, resulting in accurate provirus excision in the absence of cytopathic effects. Moreover, pronounced Tre-mediated antiviral effects are demonstrated in vivo, particularly in humanized Rag2â»/â»Î³câ»/â» mice engrafted with either Tre-transduced primary CD4⺠T cells, or Tre-transduced CD34⺠hematopoietic stem and progenitor cells (HSC). Taken together, our data support the use of Tre-recombinase in novel therapy strategies aiming to provide a cure for HIV.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Terapia Genética
/
Infecciones por VIH
/
Duplicado del Terminal Largo de VIH
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VIH-1
/
Provirus
/
Integrasas
Límite:
Animals
/
Humans
Idioma:
En
Revista:
PLoS Pathog
Año:
2013
Tipo del documento:
Article
País de afiliación:
Alemania
Pais de publicación:
Estados Unidos