A nucleolar TAR decoy inhibitor of HIV-1 replication
AUTOR(ES)
Michienzi, Alessandro
FONTE
National Academy of Sciences
RESUMO
Tat is a critical regulatory factor in HIV-1 gene expression. It mediates the transactivation of transcription from the HIV-1 LTR by binding to the transactivation response (TAR) element in a complex with cyclin T1. Because of its critical and early role in HIV gene expression, Tat and its interaction with the TAR element constitute important therapeutic targets for the treatment of HIV-1 infection. Based on the known nucleolar localization properties of Tat, we constructed a chimeric small nucleolar RNA-TAR decoy that localizes to the nucleoli of human cells and colocalizes in the nucleolus with a Tat-enhanced GFP fusion protein. When the chimeric RNA was stably expressed in human T lymphoblastoid CEM cells it potently inhibited HIV-1 replication. These results demonstrate that the nucleolar trafficking of Tat is critical for HIV-1 replication and suggests a role for the nucleolus in HIV-1 viral replication.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=137834Documentos Relacionados
- A small circular TAR RNA decoy specifically inhibits Tat-activated HIV-1 transcription.
- An inhibitor of the Tat/TAR RNA interaction that effectively suppresses HIV-1 replication
- Identification of a novel HIV-1 TAR RNA bulge binding protein.
- Ribozyme-mediated inhibition of HIV 1 suggests nucleolar trafficking of HIV-1 RNA
- Evolution of a disrupted TAR RNA hairpin structure in the HIV-1 virus.