Our knowledge of hepatitis C virus (HCV) dates only from by several groups, thereby establishing that it was caused by a transmissible agent. The chimpanzee provided a means of 1975, when non-A, non-B hepatitis was first recognized. It was not until 1989 that the genome of the virus was first characterizing the transmissible agent by classical virological methods. By determining the infectivity titer of standard cloned and sequenced, and expressed viral antigens used to develop serological assays for screening and diagnosis. HCV pools of plasma containing the virus and subjecting aliquots to various treatments, it was established that non-A, non-B is in a separate genus of the virus family Flaviviridae. It is a spherical enveloped virus of approximately 50 nm in diame-hepatitis virus contained essential lipids (and was therefore enveloped) and had a diameter of approximately 30 to 60 ter. Its genome is a single-stranded linear RNA molecule of positive sense and consists of a 5 noncoding region, a single nm. 2,3 However, it was not until 1989 that the genome of the agent was cloned and characterized and diagnostic tests large open reading frame, and a 3 noncoding region. The open reading frame encodes at least three structural and six were first developed. 4,5 Non-A, non-B hepatitis virus was subsequently renamed hepatitis C virus (HCV). Because its nonstructural proteins. The genome is characterized by significant genetic heterogeneity, based on which HCV isolates can biological and molecular characteristics were most closely related to viruses of the family Flaviviridae, it was subse-be classified into six major genotypes and more than 50 subtypes. Even individual isolates of HCV are genetically hetero-quently classified in a separate genus in this family. 6 HCV also shares slight sequence identity with other members of geneous (quasispecies diversity). Genetic heterogeneity of HCV is greatest in the amino-terminal end of the second this virus family, especially the pestiviruses. 7 The pestiviruses, flaviviruses, and HCV now comprise separate genera envelope protein (hypervariable region 1). This region may represent a neutralization epitope that is under selective pres-within the Flaviviridae. These are named Pestivirus, Flavivirus, and Hepacivirus, respectively. sure from the host's humoral immune response. Infection with HCV proceeds to chronicity in more than 80% of cases, and NATURE OF THE VIRION even recovery does not protect against subsequent re-exposure to the virus. The development of a broadly protective HCV is a spherical enveloped virus of approximately 50 vaccine against HCV will therefore require a better undernm in diameter. 8 Virus recovered during the acute phase of standing of the molecular biology and immune response to infection from the plasma of naturally infected patients and this virus. (HEPATOLOGY 1997;26(Suppl 1):11S-14S.)
experimentally infected chimpanzees has a buoyant density of approximately 1.06 g/cm 3 in sucrose. 9 In contrast, HCV Before 1975, only two hepatitis viruses were recognized: recovered from cell culture after replication in vitro has a hepatitis B virus (serum hepatitis virus) and hepatitis A virus buoyant density of 1.12 g/cm 3 in sucrose. 10 The lower density (infectious hepatitis virus). Diagnostic tests for hepatitis B of the serum-derived virus has been ascribed to its association were first developed in 1964 and for hepatitis A in 1973. with serum low-density lipoproteins, which appear to be Shortly after the diagnostic tests for hepatitis A were develbound to the virus. 11 These lipoproteins may facilitate entry oped, they were applied to sera from patients with non-B of HCV into hepatocytes by endocytosis. HCV recovered hepatitis acquired after transfusion. None of the cases was from chronically infected individuals has a buoyant density found to have been caused by hepatitis A, and such cases of approximately 1.17 g/cm 3 in sucrose. 9 Such a higher denwere termed non-A, non-B hepatitis. 1 At that time, non-A, sity virus has been shown to be associated with antibody non-B hepatitis accounted for as many as two thirds of transbound to the virus in antigen-antibody complexes. The assofusion-associated hepatitis cases. The agent and disease of ciation of HCV with low-density lipoproteins on the one non-A, non-B hepatitis became the subject of intensive rehand and with antibody on the other may be important clues search. The disease was transmitted to chimpanzees in 1978 to the pathogenesis and natural history of HCV infection.