The genome of a non-A, non-B INANB, hepatitis virus was discovered recently using a recombinant complementary DNA (cDNA) approach (1). It was termed the hepatitis C virus (HCV), and a specific diagnostic tool for circulating HCV antibody (anti-HCVI was developed using purified viral polypeptide derived from recombinant yeast expressing a small part of the HCV genome (2). Numerous data obtained using this immunoassay indicate that HCV is the predominant cause of posttransfusion NANB hepatitis around the world 12-7). Anti-HCV is associated with most community-acquired NANB hepatitis cases in the United States (2, 8 ) and Western Europe (4. 9, 10) and is a major cause of cryptogenic chronic liver disease in Italy (11). In addition, anti-HCV is associated with most cases of HCC in Japan (12, 131, Italy 110) and Spain (14). Hence, HCV is a major etiological agent of NANB hepatitis, chronic liver disease and HCC around the world. This article reviews the molecular biology of HCV and discusses its implications in diagnosing. treating and controlling HCV disease.
STRUCTURE AND FUNCTION OF THE HCV GENOME
The virus contains a positive-stranded RNA genome comprising approximately 9,400 nucleotides tnt 1 ( 1, 15-17). This sequence contains a single, large translational open-reading frame (ORF) that spans almost the entire genome and could encode a large viral polypeptide of either 3,011 (15) or 3,010 116, 17) amino acids, beginning with the first methionine codon of the ORF.
A 5' terminal region of 324 to 341 nt precedes the large coding sequence and contains three 116-18) or four ( 15.
- minute ORFs that could encode peptides of up to 28 amino acids, each begmning with a methionine residue.
It is unknown whether ribosomes translate these small 5' ORFs before translation of the large polypeptide. However, the 5' terminal region represents the most highly conserved sequence among different viral isolates (15)(16)(17)(18)(19); this suggests that it may play a very important regulatory role during viral replication. perhaps at the Address reprint requests to. Mtcliittal f Iouphtoti. 1% I) . Directtit.. NAN13 Hepatitis Research. Chiron Corp Emei-vvilk~. ( ' A 94608