Expression and identification of hepatitis C virus polyprotein cleavage products
- PMID: 7679746
- PMCID: PMC237508
- DOI: 10.1128/JVI.67.3.1385-1395.1993
Expression and identification of hepatitis C virus polyprotein cleavage products
Abstract
Hepatitis C virus (HCV) is the major cause of transfusion-acquired non-A, non-B hepatitis. HCV is an enveloped positive-sense RNA virus which has been classified as a new genus in the flavivirus family. Like the other two genera in this family, the flaviviruses and the pestiviruses, HCV polypeptides appear to be produced by translation of a long open reading frame and subsequent proteolytic processing of this polyprotein. In this study, a cDNA clone encompassing the long open reading frame of the HCV H strain (3,011 amino acid residues) has been assembled and sequenced. This clone and various truncated derivatives were used in vaccinia virus transient-expression assays to map HCV-encoded polypeptides and to study HCV polyprotein processing. HCV polyproteins and cleavage products were identified by using convalescent human sera and a panel of region-specific polyclonal rabbit antisera. Similar results were obtained for several mammalian cell lines examined, including the human HepG2 hepatoma line. The data indicate that at least nine polypeptides are produced by cleavage of the HCV H strain polyprotein. Putative structural proteins, located in the N-terminal one-fourth of the polyprotein, include the capsid protein C (21 kDa) followed by two possible virion envelope proteins, E1 (31 kDa) and E2 (70 kDa), which are heavily modified by N-linked glycosylation. The remainder of the polyprotein probably encodes nonstructural proteins including NS2 (23 kDa), NS3 (70 kDa), NS4A (8 kDa), NS4B (27 kDa), NS5A (58 kDa), and NS5B (68 kDa). An 82- to 88-kDa glycoprotein which reacted with both E2 and NS2-specific HCV antisera was also identified (called E2-NS2). Preliminary results suggest that a fraction of E1 is associated with E2 and E2-NS2 via disulfide linkages.
Similar articles
-
Characterization of the hepatitis C virus-encoded serine proteinase: determination of proteinase-dependent polyprotein cleavage sites.J Virol. 1993 May;67(5):2832-43. doi: 10.1128/JVI.67.5.2832-2843.1993. J Virol. 1993. PMID: 8386278 Free PMC article.
-
NS3 is a serine protease required for processing of hepatitis C virus polyprotein.J Virol. 1993 Jul;67(7):4017-26. doi: 10.1128/JVI.67.7.4017-4026.1993. J Virol. 1993. PMID: 7685406 Free PMC article.
-
Kinetic and structural analyses of hepatitis C virus polyprotein processing.J Virol. 1994 Aug;68(8):5045-55. doi: 10.1128/JVI.68.8.5045-5055.1994. J Virol. 1994. PMID: 8035505 Free PMC article.
-
Processing and functions of Hepatitis C virus proteins.Intervirology. 1999;42(2-3):145-52. doi: 10.1159/000024973. Intervirology. 1999. PMID: 10516468 Review.
-
Processing pathways of the hepatitis C virus proteins.J Hepatol. 1996;24(2 Suppl):11-9. J Hepatol. 1996. PMID: 8836884 Review.
Cited by
-
Hepatitis C Virus and Molecular Mimicry.Pathogens. 2024 Jun 22;13(7):527. doi: 10.3390/pathogens13070527. Pathogens. 2024. PMID: 39057754 Free PMC article. Review.
-
Characterization of a multipurpose NS3 surface patch coordinating HCV replicase assembly and virion morphogenesis.PLoS Pathog. 2022 Oct 10;18(10):e1010895. doi: 10.1371/journal.ppat.1010895. eCollection 2022 Oct. PLoS Pathog. 2022. PMID: 36215335 Free PMC article.
-
Hepatocytes infected with hepatitis C virus change immunological features in the liver microenvironment.Clin Mol Hepatol. 2023 Jan;29(1):65-76. doi: 10.3350/cmh.2022.0032. Epub 2022 Aug 12. Clin Mol Hepatol. 2023. PMID: 35957546 Free PMC article. Review.
-
Epidemiology, risk factors, and pathogenesis associated with a superbug: A comprehensive literature review on hepatitis C virus infection.SAGE Open Med. 2022 Jun 29;10:20503121221105957. doi: 10.1177/20503121221105957. eCollection 2022. SAGE Open Med. 2022. PMID: 35795865 Free PMC article. Review.
-
Direct-Acting Antiviral Agents for Hepatitis C Virus Infection-From Drug Discovery to Successful Implementation in Clinical Practice.Viruses. 2022 Jun 17;14(6):1325. doi: 10.3390/v14061325. Viruses. 2022. PMID: 35746796 Free PMC article. Review.
References
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases