New Insights into Structure and Replication of the Hepatitis C Virus and Clinical Implications

被引:61
作者
Poenisch, Marion [1 ]
Bartenschlager, Ralf [1 ]
机构
[1] Heidelberg Univ, Dept Infect Dis, D-69120 Heidelberg, Germany
关键词
STAT-C; NS3; protease; NS5A protein; NS5B RNA-dependent RNA polymerase; miR-122; cyclophilin A; DEPENDENT RNA-POLYMERASE; NONSTRUCTURAL PROTEIN 5A; 3' NONTRANSLATED REGION; CIS-ACTING REPLICATION; LIVER-CHIMERIC MICE; CORE PROTEIN; LOW-DENSITY; CRYSTAL-STRUCTURE; SUBCELLULAR-LOCALIZATION; NS3; PROTEASE;
D O I
10.1055/s-0030-1267535
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
With the advent of efficient systems to propagate the hepatitis C virus (HCV) in cultured cells important new discoveries have been made. For instance, several molecules required for HCV infection of hepatocytes have been identified and first insights into the entry pathway have been gained. Ribonucleic acid (RNA) replication and virion assembly were found to be tightly linked to lipid metabolism and numerous host factors contributing to viral replication have been identified. Some of them such as cyclophilin A or micro-RNA-122 are attractive targets for antiviral therapy as are the viral serine-type protease residing in nonstructural protein 3 (NS3) and the NS5B RNA-dependent RNA polymerase. More recently, the viral phosphoprotein NS5A emerged as an additional and very promising target for selective therapy. These results illustrate the great progress that has been made in the HCV field and how this knowledge can be used to devise innovative strategies to counteract this pathogen.
引用
收藏
页码:333 / 347
页数:15
相关论文
共 202 条
[1]   Hepatitis C virus and other Flaviviridae viruses enter cells via low density lipoprotein receptor [J].
Agnello, V ;
Abel, G ;
Elfahal, M ;
Knight, GB ;
Zhang, QX .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (22) :12766-12771
[2]   Critical role of virion-associated cholesterol and sphingolipid in hepatitis C virus infection [J].
Aizaki, Hideki ;
Morikawa, Kenichi ;
Fukasawa, Masayoshi ;
Hara, Hiromichi ;
Inoue, Yasushi ;
Tani, Hideki ;
Saito, Kyoko ;
Nishijima, Masahiro ;
Hanada, Kentaro ;
Matsuura, Yoshiharu ;
Lai, Michael A. C. ;
Miyamura, Tatsuo ;
Wakita, Takaji ;
Suzuki, Tetsuro .
JOURNAL OF VIROLOGY, 2008, 82 (12) :5715-5724
[3]   Epidemiology of hepatitis C virus infection [J].
Alter, Miriam J. .
WORLD JOURNAL OF GASTROENTEROLOGY, 2007, 13 (17) :2436-2441
[4]   Epidemiology of hepatitis C [J].
Alter, MJ .
EUROPEAN JOURNAL OF GASTROENTEROLOGY & HEPATOLOGY, 1996, 8 (04) :319-323
[5]   A haplotype map of the human genome [J].
Altshuler, D ;
Brooks, LD ;
Chakravarti, A ;
Collins, FS ;
Daly, MJ ;
Donnelly, P ;
Gibbs, RA ;
Belmont, JW ;
Boudreau, A ;
Leal, SM ;
Hardenbol, P ;
Pasternak, S ;
Wheeler, DA ;
Willis, TD ;
Yu, FL ;
Yang, HM ;
Zeng, CQ ;
Gao, Y ;
Hu, HR ;
Hu, WT ;
Li, CH ;
Lin, W ;
Liu, SQ ;
Pan, H ;
Tang, XL ;
Wang, J ;
Wang, W ;
Yu, J ;
Zhang, B ;
Zhang, QR ;
Zhao, HB ;
Zhao, H ;
Zhou, J ;
Gabriel, SB ;
Barry, R ;
Blumenstiel, B ;
Camargo, A ;
Defelice, M ;
Faggart, M ;
Goyette, M ;
Gupta, S ;
Moore, J ;
Nguyen, H ;
Onofrio, RC ;
Parkin, M ;
Roy, J ;
Stahl, E ;
Winchester, E ;
Ziaugra, L ;
Shen, Y .
NATURE, 2005, 437 (7063) :1299-1320
[6]   The functions of animal microRNAs [J].
Ambros, V .
NATURE, 2004, 431 (7006) :350-355
[7]   Targeting lipid metabolism in the treatment of hepatitis C virus infection [J].
Amemiya, Fumitake ;
Maekawa, Shinya ;
Itakura, Yoshie ;
Kanayama, Asuka ;
Matsui, Akira ;
Takano, Shinichi ;
Yamaguchi, Tatsuya ;
Itakura, Jun ;
Kitamura, Takatoshi ;
Inoue, Taisuke ;
Sakamoto, Minoru ;
Yamauchi, Kozue ;
Okada, Shunichi ;
Yamashita, Atsuya ;
Sakamoto, Naoya ;
Itoh, Masahiko ;
Enomoto, Nobuyuki .
JOURNAL OF INFECTIOUS DISEASES, 2008, 197 (03) :361-370
[8]   Characterization of low- and very-low-density hepatitis C virus RNA-containing particles [J].
André, P ;
Komurian-Pradel, F ;
Deforges, S ;
Perret, M ;
Berland, JL ;
Sodoyer, M ;
Pol, S ;
Bréchot, C ;
Paranhos-Baccalà, G ;
Lotteau, V .
JOURNAL OF VIROLOGY, 2002, 76 (14) :6919-6928
[9]   Hepatitis C virus particles and lipoprotein metabolism [J].
André, P ;
Perlemuter, G ;
Budkowska, A ;
Bréchot, C ;
Lotteau, V .
SEMINARS IN LIVER DISEASE, 2005, 25 (01) :93-104
[10]   Mutational analysis of hepatitis C virus nonstructural protein 5A: Potential role of differential phosphorylation in RNA replication and identification of a genetically flexible domain [J].
Appel, N ;
Pietschmann, T ;
Bartenschlager, R .
JOURNAL OF VIROLOGY, 2005, 79 (05) :3187-3194