La protein required for internal ribosome entry site-directed translation is a potential therapeutic target for hepatitis C virus replication.
J Infect Dis
; 202(1): 75-85, 2010 Jul 01.
Article
em En
| MEDLINE
| ID: mdl-20497049
ABSTRACT
BACKGROUND:
Translation of the hepatitis C virus (HCV) is mediated by an internal ribosome entry site (IRES). Here, we analyzed the functional relevance of La protein for replication of HCV using an infectious HCV clone, JFH-1.METHODS:
A single-nucleotide mutation from A to U was introduced at the 338th nucleotide in the stem-loop domain IV structure of HCV IRES, which stabilized stem-loop IV and abolished translation and replication of JFH-1 almost completely.RESULTS:
During JFH-1 replication, translation initiation factors required for HCV IRES activity, including La protein, polypyrimidine tract binding protein (PTB), PSMA7, and PCBP2, were significantly induced in Huh-7.5 cells. Interestingly, JFH-1 infection increased telomerase activity and induced the expression of human telomerase RNA (hTR) in Huh-7.5 cells. In 37 tissue specimens from patients with chronic hepatitis C, La protein significantly correlated with the representative essential telomerase components hTR, p23, and HSP90 (P<.001). Recombinant adenovirus that expressed short-hairpin RNA against La protein successfully suppressed the levels of La protein and core protein of JFH-1 to 30% of that in the control cells.CONCLUSIONS:
HCV infection might be strongly related to telomerase activity in the liver through La protein induction. Inhibition of La protein substantially repressed JFH-1 replication; therefore, La protein is a potential therapeutic target for HCV.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Ribonucleoproteínas
/
Autoantígenos
/
Hepacivirus
Limite:
Humans
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article