The influence of intracellular keratin 8 on hepatitis C virus replication
10.16438/j.0513-4870.2016-0283
- VernacularTitle:细胞角蛋白8对丙型肝炎病毒复制的影响
- Author:
Wen-jing LI
1
;
Jian-rui LI
1
;
Meng-hao HUANG
1
;
Zhou-yi WU
1
;
Jin-hua CHEN
1
;
Hu LI
1
;
Xiao-qin LÜ
1
;
Jun-jun CHENG
1
;
Zong-gen PENG
1
Author Information
1. Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
- Publication Type:ORIGINAL ARTICLES
- Keywords:
keratin 8;
hepatitis C virus;
co-factor;
antiviral target;
host factor
- From:
Acta Pharmaceutica Sinica
2016;51(6):913-
- CountryChina
- Language:Chinese
-
Abstract:
The level of intracellular keratin 8(KRT-8) is associated with liver diseases, whose expression is increased in hepatitis C virus (HCV)-infected patients with hepatocarcinoma and in cultural cells infected with HCV. However, it is not clear whether KRT-8 will impact HCV replication. In this paper, the HCV replication was analyzed in response to high expression and silence of KRT-8. The inhibitory activities against wild-type and mutant HCV were also analyzed by silence of KRT-8 or combined with known anti-HCV drug telaprevir. Results showed that the protein level of KRT-8 was increased in proportion with the HCV replication. The high expression was found to facilitate HCV replication, while the silence of KRT-8 was able to inhibit HCV replication and enhanced the anti-HCV activity of telaprevir. It also inhibited A156T and D168V mutant HCV, which are resistant to protease inhibitors. These results suggest that KRT-8 is a co-factor for HCV replication. Down-regulation of KRT-8 can inhibit wild type and mutant HCV replication to enhance the anti-HCV activity of known anti-HCV drugs. Therefore, KRT-8 may be a new target in the development of anti-HCV agents.