Characteristics of the hepatitis C virus
- Sanjiv Chopra, MD, MACP
Sanjiv Chopra, MD, MACP
- Editor-in-Chief — Gastroenterology/Hepatology
- Section Editor — General Hepatology
- Section Editor — 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 .
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