Specific laboratory diagnosis of hepatitis types A, B and delta revealed an unrecognised form of hepatitis that was clearly unrelated to any of these three types of viruses. Surveys of post-transfusion hepatitis, after the administration of blood and blood products screened for hepatitis B by highly sensitive techniques, provided strong epidemiological evidence of 'guilt by association' of an infection of the liver referred to as non-A, non-B hepatitis.
Attempts to clone the agent ofparenterally transmitted non-A, non-B hepatitis were made from a plasma known to contain high titre of the agent by experimental transmission to nonhuman primates. Because it was not known whether the genome was DNA or RNA, a de-naturation step was included before the synthesis of complementary DNA so that either DNA or RNA could serve as a template. The resultant cDNA was then inserted into the bacteriophage expression vector X gt 11 and the libraries screened using serum from a patient with chronic non-A, non-B hepatitis. This led to the detection of a clone that was found to bind to antibodies present in the sera of patients infected with non-A, non-B hepatitis. This clone was used as a probe to detect a larger, overlapping clone in the same library. These sequences hybridised to a positive-sense RNA molecule of about 10 000 nt, which was present in the livers of infected chimpanzees but not in uninfected controls. Homologous sequences were not detected in the chimpanzee or human genomes. By employing a 'walking' technique, the newly detected overlapping clones were used as hybridisation probes to detect further virus-specific clones in the library. Thus, clones covering the entire viral genome were assembled and the completed nucleotide sequence of hepatitis C virus was determined.
Infection with Hepatitis C virus (HCV) is prevalent throughout the world, and persistent infection and chronic liver disease are common.
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