Characteristics of the hepatitis C virus
- Sanjiv Chopra, MD, MACP
Sanjiv Chopra, MD, MACP
- Editor-in-Chief — Gastroenterology/Hepatology
- Section Editor — General Hepatology; Gallbladder and Biliary Tract Disease
- Professor of Medicine
- Harvard Medical School
- Senior Consultant in Hepatology
- James Tullis Firm Chief
- Beth Israel Deaconess Medical Center
- Section Editors
- Morven S Edwards, MD
Morven S Edwards, MD
- Section Editor — Pediatric Infectious Diseases
- Professor of Pediatrics
- Baylor College of Medicine
- Adrian M Di Bisceglie, MD
Adrian M Di Bisceglie, MD
- Section Editor — Hepatitis C
- Chief of Hepatology
- Saint Louis University School of Medicine
It became apparent after the discovery of the hepatitis A and B viruses in the late 1960s and early 1970s that a large proportion of cases of acute and chronic hepatitis could not be explained by either of these agents. Another viral agent was suspected, and patients infected with this suspected agent were said to have non-A, non-B hepatitis. The agent was finally identified in 1989 when the genome of the virus was cloned and the agent was designated the hepatitis C virus (HCV) .
HCV is closely related to flaviviruses and pestiviruses. Its genetic organization and protein products classify it in the Flaviviridae family, although its diversity is great enough for it to be classified as a separate genus. HCV is not related to any of the other known hepatitis viruses; however, the recently described hepatitis G virus is a distant relative. (See "GB virus C (hepatitis G) infection".)
VIRAL GENOME AND REPLICATION
The HCV genome is a positive-sense RNA molecule of approximately 9500 nucleotides. There are highly conserved 5' and 3' untranslated regions flanking an approximately 9000 nucleotide single open reading frame which encodes a large polyprotein of about 3000 amino acids . This protein undergoes posttranslational processing by host and viral enzymes to form the structural and nonstructural proteins and enzymes of the virus.
The 5' terminus of the viral RNA is an untranslated region (5' UTR) known to be essential for replication; it contains elements felt to coordinate viral protein synthesis. It is not surprising that this region is highly conserved, and therefore serves as a useful target for amplification in diagnostic assays.
The polymerase enzyme of RNA viruses such as HCV lacks proofreading ability and is therefore unable to correct copying errors made during viral replication. Many of these nucleotide changes result in a nonfunctional genome or a replication incompetent virus (lethal mutants). However, others persist and account for the tremendous viral diversity that is characteristic of HCV. This heterogeneity is extremely important in the diagnosis of infection, pathogenesis of disease, and the response to treatment; it prevents the development of conventional vaccines, allows the virus to escape eradication by the host's immune system, and affects the completeness of the response to antiviral therapies such as interferon .
- Choo QL, Kuo G, Weiner AJ, et al. Isolation of a cDNA clone derived from a blood-borne non-A, non-B viral hepatitis genome. Science 1989; 244:359.
- Major ME, Feinstone SM. The molecular virology of hepatitis C. Hepatology 1997; 25:1527.
- Farci P, Alter HJ, Govindarajan S, et al. Lack of protective immunity against reinfection with hepatitis C virus. Science 1992; 258:135.
- Simmonds P. Variability of hepatitis C virus. Hepatology 1995; 21:570.
- Farci P, Shimoda A, Wong D, et al. Prevention of hepatitis C virus infection in chimpanzees by hyperimmune serum against the hypervariable region 1 of the envelope 2 protein. Proc Natl Acad Sci U S A 1996; 93:15394.
- González-Peralta RP, Qian K, She JY, et al. Clinical implications of viral quasispecies heterogeneity in chronic hepatitis C. J Med Virol 1996; 49:242.
- Sakai A, Kaneko S, Honda M, et al. Quasispecies of hepatitis C virus in serum and in three different parts of the liver of patients with chronic hepatitis. Hepatology 1999; 30:556.
- Tanaka Y, Hanada K, Hanabusa H, et al. Increasing genetic diversity of hepatitis C virus in haemophiliacs with human immunodeficiency virus coinfection. J Gen Virol 2007; 88:2513.
- Weiner AJ, Geysen HM, Christopherson C, et al. Evidence for immune selection of hepatitis C virus (HCV) putative envelope glycoprotein variants: potential role in chronic HCV infections. Proc Natl Acad Sci U S A 1992; 89:3468.
- Lai ME, Mazzoleni AP, Argiolu F, et al. Hepatitis C virus in multiple episodes of acute hepatitis in polytransfused thalassaemic children. Lancet 1994; 343:388.
- Simmonds P, Alberti A, Alter HJ, et al. A proposed system for the nomenclature of hepatitis C viral genotypes. Hepatology 1994; 19:1321.
- Smith DB, Bukh J, Kuiken C, et al. Expanded classification of hepatitis C virus into 7 genotypes and 67 subtypes: updated criteria and genotype assignment web resource. Hepatology 2014; 59:318.
- Simmonds P, Bukh J, Combet C, et al. Consensus proposals for a unified system of nomenclature of hepatitis C virus genotypes. Hepatology 2005; 42:962.
- Lau JY, Davis GL, Prescott LE, et al. Distribution of hepatitis C virus genotypes determined by line probe assay in patients with chronic hepatitis C seen at tertiary referral centers in the United States. Hepatitis Interventional Therapy Group. Ann Intern Med 1996; 124:868.
- Dusheiko G, Schmilovitz-Weiss H, Brown D, et al. Hepatitis C virus genotypes: an investigation of type-specific differences in geographic origin and disease. Hepatology 1994; 19:13.
- Messina JP, Humphreys I, Flaxman A, et al. Global distribution and prevalence of hepatitis C virus genotypes. Hepatology 2015; 61:77.