HEXIM1-Tat chimera inhibits HIV-1 replication.
PLoS Pathog
; 14(11): e1007402, 2018 11.
Article
en En
| MEDLINE
| ID: mdl-30395647
ABSTRACT
Transcription of HIV provirus is a key step of the viral cycle, and depends on the recruitment of the cellular positive transcription elongation factor b (P-TEFb) to the HIV promoter. The viral transactivator Tat can displace P-TEFb from the 7SK small nuclear ribonucleoprotein, where it is bound and inactivated by HEXIM1, and bring it to TAR, which allows the stalled RNA polymerase II to transition to successful transcription elongation. In this study, we designed a chimeric inhibitor of HIV transcription by combining functional domains from HEXIM1 and Tat. The chimera (HT1) potently inhibited gene expression from the HIV promoter, by competing with Tat for TAR and P-TEFb binding, while keeping the latter inactive. HT1 inhibited spreading infection as well as viral reactivation in lymphocyte T cell line models of HIV latency, with little effect on cellular transcription and metabolism. This proof-of-concept study validates an innovative approach to interfering with HIV transcription via peptide mimicry and competition for RNA-protein interactions. HT1 represents a new candidate for HIV therapy, or HIV cure via the proposed block and lock strategy.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Replicación Viral
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Proteínas Recombinantes de Fusión
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Infecciones por VIH
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VIH-1
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Proteínas de Unión al ARN
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Productos del Gen tat del Virus de la Inmunodeficiencia Humana
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
PLoS Pathog
Año:
2018
Tipo del documento:
Article
País de afiliación:
Estados Unidos