Hepatitis C Virus Proteins: From Structure to Function

Chapter
Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 369)

Abstract

Great progress has been made over the past years in elucidating the structure and function of the hepatitis C virus (HCV) proteins, most of which are now actively being pursued as antiviral targets. The structural proteins, which form the viral particle, include the core protein and the envelope glycoproteins E1 and E2. The nonstructural proteins include the p7 viroporin, the NS2 protease, the NS3-4A complex harboring protease and NTPase/RNA helicase activities, the NS4B and NS5A proteins, and the NS5B RNA-dependent RNA polymerase. NS4B is a master organizer of replication complex formation while NS5A is a zinc-containing phosphoprotein involved in the regulation of HCV RNA replication versus particle production. Core to NS2 make up the assembly module while NS3 to NS5B represent the replication module (replicase). However, HCV proteins exert multiple functions during the viral life cycle, and these may be governed by different structural conformations and/or interactions with viral and/or cellular partners. Remarkably, each viral protein is anchored to intracellular membranes via specific determinants that are essential to protein function in the cell. This review summarizes current knowledge of the structure and function of the HCV proteins and highlights recent advances in the field.

Keywords

Nonstructural Protein Signal Peptide Peptidase Alternative Reading Frame Protein Functional Replication Complex 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Abbreviations

aa

Amino acid

AH

Amphipathic α-helix

CHV

Canine hepacivirus

CK

Casein kinase

CsA

Cyclosporin A

CypA

Cyclophilin A

DHPC

1,2-diheptanol-sn-glycero-3-phosphocholine

E

Envelope glycoprotein

ER

Endoplasmic reticulum

GBV-B

GB virus B

HCV

Hepatitis C virus

HVR

Hypervariable region

igVR

Intergenotypic variable domain

IRES

Internal ribosome entry site

ISDR

Interferon sensitivity determining region

LCS

Low complexity sequence

LD

Lipid droplet

MD

Molecular dynamics

NCR

Noncoding region

NMR

Nuclear magnetic resonance

NS

Nonstructural protein

ORF

Open reading frame

PI4KIII

Phosphatidylinositol 4-kinase III

PI4P

Phosphatidylinositol 4-phosphate

POPC

1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine

RdRp

RNA-dependent RNA polymerase

SPP

Signal peptide peptidase

TMD

Transmembrane domain

Notes

Acknowledgments

Research in the authors’ laboratories is supported by the Swiss National Science Foundation, the French Centre National de la Recherche Scientifique, and the French National Agency for Research on AIDS and Viral Hepatitis.

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© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  1. 1.Division of Gastroenterology and Hepatology, Centre Hospitalier Universitaire VaudoisUniversity of LausanneLausanneSwitzerland
  2. 2.Institut de Biologie et Chimie des Protéines, Bases Moléculaires et Structurales des Systèmes Infectieux, UMR 5086CNRS, University of LyonLyonFrance

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