The Discovery of the Hepatitis C Virus
After a 6-year intensive search for the causative agent of parenteral non-A, non-B hepatitis using a large variety of pre-PCR molecular biological, immunological, and virological methods, HCV was discovered using a cDNA immunoscreening method in which infectious chimpanzee plasma was used as the source of cloning material and NANBH patient sera as a presumptive source of NANBH-specific antibodies. Clone 5-1-1 and overlapping clones were shown to be extrachromosomal in origin, to be derived from a large single-stranded RNA found only in NANBH materials and which directly encoded an antigen shown to specifically bind antibodies in most parenteral NANBH-infected chimpanzees and patients. The nucleotide sequence of the RNA genome exhibited low homology with flaviviruses which in combination proved that HCV was the major cause of blood-borne NANBH and that it was a distant relative of the Flaviviridae family. Since 1990, a series of HCV-specific antibody- and RNA-detecting blood screening tests have effectively eliminated posttransfusion HCV infections. Subsequent decades of research by the field into the viral life cycle and the development of direct-acting antivirals have now led to HCV becoming the first curable, chronically infecting virus of man. It is now important to focus on a prophylactic vaccine to curtail this global epidemic.
KeywordsBlood-borne NANBH Flaviviridae HCV HCV blood tests HCV discovery HCV identification Hepatitis C virus Non-A, non-B hepatitis
Compliance with Ethical Standards
Funding This study was funded by the Canada Excellence in Research Chairs program, Alberta Innovates and the Li Ka Shing Institute of Virology.
Conflict of Interest
Author is a director and stock holder of Aurora Vaccines Inc.
All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures performed in the studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Informed consent was obtained from all individual participants included in the study.
- 1.Houghton M (2000) Identification of the hepatitis C virus. Nat Med 6(10):1084–1086Google Scholar
- 4.Houghton M (2016) Towards the control of hepatitis C. In: Miyamura T, Lemon S, Walker C, Wakita T (eds) Hepatitis C virus I. Springer, TokyoGoogle Scholar
- 9.Barré-Sinoussi F, Chermann JC, Rey F, Nugeyre MT, Chamaret S, Gruest J, Dauguet C, Axler-Blin C, Vézinet-Brun F, Rouzioux C, Rozenbaum W, Montagnier L (1983) Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome (AIDS). Science 220(4599):868–871CrossRefGoogle Scholar
- 13.Bradley DW, Cook EH, Maynard JE, McCaustland KA, Ebert JW, Dolana GH, Petzel RA, Kantor RJ, Heilbrunn A, Fields HA, Murphy BL (1979) Experimental infection of chimpanzees with antihemophilic (factor VIII) materials: recovery of virus-like particles associated with non-A, non-B hepatitis. J Med Virol 3(4):253–269CrossRefGoogle Scholar
- 18.Wakita T, Pietschmann T, Kato T, Date T, Miyamoto M, Zhao Z, Murthy K, Habermann A, Kräusslich HG, Mizokami M, Bartenschlager R, Liang TJ (2005) Production of infectious hepatitis C virus in tissue culture from a cloned viral genome. Nat Med 11(7):791–796. Epub 2005 Jun 12. Erratum in: Nat Med. 2005 Aug;11(8):905CrossRefGoogle Scholar