CRISPR-mediated Activation of Latent HIV-1 Expression.
Mol Ther
; 24(3): 499-507, 2016 Mar.
Article
em En
| MEDLINE
| ID: mdl-26607397
ABSTRACT
Complete eradication of HIV-1 infection is impeded by the existence of cells that harbor chromosomally integrated but transcriptionally inactive provirus. These cells can persist for years without producing viral progeny, rendering them refractory to immune surveillance and antiretroviral therapy and providing a permanent reservoir for the stochastic reactivation and reseeding of HIV-1. Strategies for purging this latent reservoir are thus needed to eradicate infection. Here, we show that engineered transcriptional activation systems based on CRISPR/Cas9 can be harnessed to activate viral gene expression in cell line models of HIV-1 latency. We further demonstrate that complementing Cas9 activators with latency-reversing compounds can enhance latent HIV-1 transcription and that epigenome modulation using CRISPR-based acetyltransferases can also promote viral gene activation. Collectively, these results demonstrate that CRISPR systems are potentially effective tools for inducing latent HIV-1 expression and that their use, in combination with antiretroviral therapy, could lead to improved therapies for HIV-1 infection.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Ativação Viral
/
Regulação Viral da Expressão Gênica
/
Ativação Transcricional
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HIV-1
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Latência Viral
/
Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas
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Sistemas CRISPR-Cas
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article