Inhibition of HIV-1 replication in viral mutants with altered TAR RNA stem structures.
Virology
; 216(2): 411-7, 1996 Feb 15.
Article
em En
| MEDLINE
| ID: mdl-8607271
ABSTRACT
Human immunodeficiency virus type 1 (HIV-1) Tat-mediated trans-activation requires the structural integrity of TAR RNA and the cooperative interaction of human host cell proteins. The TAR domain, minimally required for tat response, includes the Tat binding pyrimidine bulge, the TAR RNA upper stem, and the loop sequences. However, little is known about the significance of the 5'-stem structure of TAR in the regulation of viral growth. We designed viral mutations, specifically in the TAR RNA lower stem structure, and studied their effects on the kinetics of viral growth in T-lymphocyte cell lines and in activated human peripheral blood mononuclear cells. Mutations that destabilized the lower TAR stem structure inhibited viral growth to various degrees in different CD4+ T-cells. These results suggest that the structural integrity of the lower stem structure of TAR plays an important role in viral growth, presumably by binding to specific host cell proteins that stabilize Tat-TAR interactions.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
RNA Viral
/
Repetição Terminal Longa de HIV
/
HIV-1
/
Proteínas de Ligação a RNA
/
Conformação de Ácido Nucleico
Limite:
Humans
Idioma:
En
Revista:
Virology
Ano de publicação:
1996
Tipo de documento:
Article
País de afiliação:
Estados Unidos