Introduction

Hepatitis C virus (HCV) has emerged as an important cause of viral hepatitis in children but the actual number of infected children is underestimated. Because of the ability of this virus to establish chronic progressive infection, HCV infection is now a leading indication for liver transplantation in adults. The discovery of HCV using molecular cloning techniques in 1989 has led directly to a reduction in the number of acute HCV infections, and the establishment of detection and treatment strategies.

Virology

The virus is the prototype for the Hepacivirus genus of the family Flaviviridae. The virion is about 30–60nm in diameter. The capsid is thought to be enveloped by a lipid bilayer. The envelope contains two viral glycoproteins, E1 and E2, and the nucleocapsid contained within is composed of core protein and the viral RNA genome [1].

The genome is a 9.6 kb positive, single-stranded RNA (Figure 19.1). A single open reading frame (ORF) encodes a 3011 amino acid residue polyprotein that undergoes proteolysis to yield at least 10 individual gene products. Structural proteins (core and envelope) are encoded in the 50-quarter of the genome. The structural proteins (core, E1 and E2) are processed by host peptidase, and the non-structural (NS) proteins are subsequently cleaved by virally encoded NS2-3 and NS-3 proteases. The core protein is highly conserved and may be involved in other processes such as apoptosis, intracellular signaling, transcription, and modulation of the host immune response. Protein E2 binds specifically to host CD81, suggesting that it mediates viral entry into the cell. Unlike the core protein, E1 and E2 demonstrate considerable sequence heterogeneity from different isolates. The N-terminus of E2 contains a “hypervariable” region (HVR) HVR1 that is an important viral neutralization determinant. This region is also a T-cell determinant, able to activate helper T-cell responses during HCV infection. The sequence variability of E2 may account, at least in part, for the ability of HCV to elude the host immune system and establish persistent infection. Downstream is a small integral membrane protein, p7, which appears to function as an ion channel but also appears necessary for efficient assembly, release, and production of infectious progeny virions from liver cells.