Genetic Organization and Diversity of the Hepatitis C Virus

• Published in: Proceedings of the National Academy of Sciences - PNAS 1991-03, Vol.88 (6), p.2451-2455
• Main Authors: Q.-L. Choo, Richman, K. H., Han, J. H., Berger, K., Lee, C., Dong, C., Gallegos, C., Coit, D., Medina-Selby, A., Barr, P. J., Weiner, A. J., Bradley, D. w., Kuo, G., Houghton, M.
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Amino acids; Animals; Base Sequence; Biological and medical sciences; Complementary DNA; Fundamental and applied biological sciences. Psychology; Genes, Viral; Genetic Variation; Genetics; Genomes; Hepacivirus; Hepacivirus - genetics; Hepacivirus - isolation & purification; Microbiology; Molecular Sequence Data; Nucleotide sequences; Oligonucleotide Probes; Open reading frames; Pan troglodytes; Polyproteins; Protein Conformation; Proteins; RNA; RNA, Viral - genetics; Sequence Homology, Nucleic Acid; Viral Proteins - genetics; Virology; Viruses
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.88.6.2451

The nucleotide sequence of the RNA genome of the human hepatitis C virus (HCV) has been determined from overlapping cDNA clones. The sequence (9379 nucleotides) has a single large open reading frame that could encode a viral polyprotein precursor of 3011 amino acids. While there is little overall amino acid and nucleotide sequence homology with other viruses, the 5' HCV nucleotide sequence upstream of this large open reading frame has substantial similarity to the 5' termini of pestiviral genomes. The polyprotein also has significant sequence similarity to helicases encoded by animal pestiviruses, plant potyviruses, and human flaviviruses, and it contains sequence motifs widely conserved among viral replicases and trypsin-like proteases. A basic, presumed nucleocapsid domain is located at the N terminus upstream of a region containing numerous potential N-linked glycosylation sites. These HCV domains are located in the same relative position as observed in the pestiviruses and flaviviruses and the hydrophobic profiles of all three viral polyproteins are similar. These combined data indicate that HCV is an unusual virus that is most related to the pestiviruses. Significant genome diversity is apparent within the putative 5' structural gene region of different HCV isolates, suggesting the presence of closely related but distinct viral genotypes.