Home LiteratureArticle Details
PMID: 9573256 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Long-term evolution of the hypervariable region of hepatitis C virus in a common-source-infected cohort.

Journal of virology ·Vol. 72 ·No. 6 ·1998-06-00 ·Pages 4893-905

McAllister J, Casino C, Davidson F, Power J, Lawlor E, Yap PL, Simmonds P, Smith DB

Abstract

The long-term evolution of the hepatitis C virus hypervariable region (HVR) and flanking regions of the E1 and E2 envelope proteins have been studied in a cohort of women infected from a common source of anti-D immunoglobulin. Whereas virus sequences in the infectious source were relatively homogeneous, distinct HVR variants were observed in each anti-D recipient, indicating that this region can evolve in multiple directions from the same point. Where HVR variants with dissimilar sequences were present in a single individual, the frequency of synonymous substitution in the flanking regions suggested that the lineages diverged more than a decade previously. Even where a single major HVR variant was present in an infected individual, this lineage was usually several years old. Multiple lineages can therefore coexist during long periods of chronic infection without replacement. The characteristics of amino acid substitution in the HVR were not consistent with the random accumulation of mutations and imply that amino acid replacement in the HVR was strongly constrained. Another variable region of E2 centered on codon 60 shows similar constraints, while HVR2 was relatively unconstrained. Several of these features are difficult to explain if a neutralizing immune response against the HVR is the only selective force operating on E2. The impact of PCR artifacts such as nucleotide misincorporation and the shuffling of dissimilar templates is discussed.

MeSH Terms
Amino Acid Sequence Cohort Studies Evolution, Molecular Female Hepacivirus/genetics Hepatitis C/virology Humans Molecular Sequence Data Phylogeny Sequence Analysis Viral Envelope Proteins/genetics
Chemicals
E1 protein, Hepatitis C virus Viral Envelope Proteins glycoprotein E2, Hepatitis C virus
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
McAllister J
Department of Medical Microbiology, University of Edinburgh Medical School, Edinburgh EH8 9AG, Scotland.
Casino C
Davidson F
Power J
Lawlor E
Yap P L
Simmonds P
Smith D B
References (52)
52 references, click to expand
  1. Variability of hepatitis C virus.
    Hepatology. 1995 Feb;21(2):570-83 PMID: 7531173
  2. Sequence analysis of hepatitis C virus variants producing discrepant results with two different genotyping assays.
    J Med Virol. 1997 Nov;53(3):237-44 PMID: 9365889
  3. Molecular epidemiology of an outbreak of infection with hepatitis C virus in recipients of anti-D immunoglobulin.
    Lancet. 1995 May 13;345(8959):1211-3 PMID: 7739308
  4. Antibodies in human sera specific to hypervariable region 1 of hepatitis C virus can block viral attachment.
    Virology. 1995 Apr 20;208(2):653-61 PMID: 7538251
  5. Occurrence of antibodies reactive with more than one variant of the putative envelope glycoprotein (gp70) hypervariable region 1 in viremic hepatitis C virus-infected patients.
    J Virol. 1995 Jul;69(7):4407-12 PMID: 7539508
  6. Quasispecies of hepatitis C virus and genetic drift of the hypervariable region in chronic type C hepatitis.
    J Infect Dis. 1995 Jul;172(1):261-4 PMID: 7797927
  7. Comparison of full-length sequences of interferon-sensitive and resistant hepatitis C virus 1b. Sensitivity to interferon is conferred by amino acid substitutions in the NS5A region.
    J Clin Invest. 1995 Jul;96(1):224-30 PMID: 7542279
  8. Dynamic analysis of heterogeneous hepatitis C virus populations by direct solid-phase sequencing.
    J Clin Microbiol. 1995 Jul;33(7):1870-4 PMID: 7665662
  9. Lymphoproliferative responses to hepatitis C virus core, E1, E2, and NS3 in patients with chronic hepatitis C infection treated with interferon alfa.
    Hepatology. 1996 Jan;23(1):8-16 PMID: 8550052
  10. Transmission of hepatitis C virus by a cardiac surgeon.
    N Engl J Med. 1996 Feb 29;334(9):555-60 PMID: 8569822
  11. Hepatitis C in human immunodeficiency virus-coinfected patients: increased variability in the hypervariable envelope coding domain.
    Hepatology. 1996 Apr;23(4):688-94 PMID: 8666318
  12. Deficiency of antibody response to hypervariable region of hepatitis C virus in patients with chronic hepatitis C.
    J Hepatol. 1996 Jun;24(6):649-57 PMID: 8835738
  13. The natural history of hepatitis C: clinical experiences.
    J Hepatol. 1996;24(2 Suppl):52-4 PMID: 8836889
  14. Patients infected with the same hepatitis C virus strain display different kinetics of the isolate-specific antibody response.
    J Infect Dis. 1997 Jan;175(1):26-31 PMID: 8985192
  15. Prevention of hepatitis C virus infection in chimpanzees by hyperimmune serum against the hypervariable region 1 of the envelope 2 protein.
    Proc Natl Acad Sci U S A. 1996 Dec 24;93(26):15394-9 PMID: 8986822
  16. Human immunodeficiency virus-infected individuals contain provirus in small numbers of peripheral mononuclear cells and at low copy numbers.
    J Virol. 1990 Feb;64(2):864-72 PMID: 2296085
  17. DNA recombination during PCR.
    Nucleic Acids Res. 1990 Apr 11;18(7):1687-91 PMID: 2186361
  18. Variable and hypervariable domains are found in the regions of HCV corresponding to the flavivirus envelope and NS1 proteins and the pestivirus envelope glycoproteins.
    Virology. 1991 Feb;180(2):842-8 PMID: 1846505
  19. Hypervariable regions in the putative glycoprotein of hepatitis C virus.
    Biochem Biophys Res Commun. 1991 Feb 28;175(1):220-8 PMID: 1847805
  20. Nucleotide sequence and mutation rate of the H strain of hepatitis C virus.
    Proc Natl Acad Sci U S A. 1991 Apr 15;88(8):3392-6 PMID: 1849654
  21. Human immunodeficiency virus genetic variation that can escape cytotoxic T cell recognition.
    Nature. 1991 Dec 12;354(6353):453-9 PMID: 1721107
  22. Evolution of the H3 influenza virus hemagglutinin from human and nonhuman hosts.
    J Virol. 1992 Feb;66(2):1129-38 PMID: 1731092
  23. Evidence for immune selection of hepatitis C virus (HCV) putative envelope glycoprotein variants: potential role in chronic HCV infections.
    Proc Natl Acad Sci U S A. 1992 Apr 15;89(8):3468-72 PMID: 1314389
  24. Marked sequence diversity in the putative envelope proteins of hepatitis C viruses.
    Virus Res. 1992 Feb;22(2):107-23 PMID: 1314471
  25. Molecular cloning of hepatitis C virus genome from a single Japanese carrier: sequence variation within the same individual and among infected individuals.
    Virus Res. 1992 Apr;23(1-2):39-53 PMID: 1318627
  26. The degree of variability in the amino terminal region of the E2/NS1 protein of hepatitis C virus correlates with responsiveness to interferon therapy in viremic patients.
    Hepatology. 1992 Sep;16(3):619-24 PMID: 1380477
  27. Genetic drift of hepatitis C virus during an 8.2-year infection in a chimpanzee: variability and stability.
    Virology. 1992 Oct;190(2):894-9 PMID: 1325713
  28. Intrahepatic cytotoxic T lymphocytes specific for hepatitis C virus in persons with chronic hepatitis.
    J Immunol. 1992 Nov 15;149(10):3339-44 PMID: 1385523
  29. Humoral immune response to hypervariable region 1 of the putative envelope glycoprotein (gp70) of hepatitis C virus.
    J Virol. 1993 Jul;67(7):3923-30 PMID: 7685404
  30. A unique, predominant hepatitis C virus variant found in an infant born to a mother with multiple variants.
    J Virol. 1993 Jul;67(7):4365-8 PMID: 8389933
  31. A structurally flexible and antigenically variable N-terminal domain of the hepatitis C virus E2/NS1 protein: implication for an escape from antibody.
    Virology. 1993 Jul;195(1):297-301 PMID: 7686313
  32. Hypervariable 5'-terminus of hepatitis C virus E2/NS1 encodes antigenically distinct variants.
    J Med Virol. 1993 Jun;40(2):150-6 PMID: 7689636
  33. Dynamics of genome change in the E2/NS1 region of hepatitis C virus in vivo.
    Virology. 1993 Dec;197(2):659-68 PMID: 8249288
  34. Sequential change of the hypervariable region of the hepatitis C virus genome in acute infection.
    J Med Virol. 1994 Jan;42(1):103-8 PMID: 7508488
  35. Genetic alteration of the hepatitis C virus hypervariable region obtained from an asymptomatic carrier.
    Int J Cancer. 1994 Jan 15;56(2):204-7 PMID: 8314302
  36. Neutralizing antibodies against hepatitis C virus and the emergence of neutralization escape mutant viruses.
    J Virol. 1994 Mar;68(3):1494-500 PMID: 8107212
  37. Hypervariable region of hepatitis C virus envelope glycoprotein (E2/NS1) in an agammaglobulinemic patient.
    Gastroenterology. 1994 Apr;106(4):1072-5 PMID: 8143975
  38. ODEN: a program package for molecular evolutionary analysis and database search of DNA and amino acid sequences.
    Comput Appl Biosci. 1994 Feb;10(1):11-2 PMID: 8193950
  39. Genetic alterations of the putative envelope proteins encoding region of the hepatitis C virus in the progression to relapsed phase from acute hepatitis: humoral immune response to hypervariable region 1.
    Int J Cancer. 1994 Jun 1;57(5):664-70 PMID: 7515022
  40. Genetic drift in hypervariable region 1 of the viral genome in persistent hepatitis C virus infection.
    J Virol. 1994 Aug;68(8):4776-84 PMID: 7518526
  41. Frequent reinfection and reactivation of hepatitis C virus genotypes in multitransfused hemophiliacs.
    J Infect Dis. 1994 Oct;170(4):1018-22 PMID: 7930698
  42. Hepatitis C viraemia in recipients of Irish intravenous anti-D immunoglobulin.
    Lancet. 1994 Oct 22;344(8930):1166-7 PMID: 7934528
  43. Evolution and selection of hepatitis C virus variants in patients with chronic hepatitis C.
    Virology. 1994 Nov 15;205(1):161-9 PMID: 7975211
  44. Sequence variability in the env-coding region of hepatitis C virus isolated from patients infected during a single source outbreak.
    Arch Virol. 1994;137(1-2):25-34 PMID: 7979995
  45. Sequence evolution of the hypervariable region in the putative envelope region E2/NS1 of hepatitis C virus is correlated with specific humoral immune responses.
    J Virol. 1995 Feb;69(2):773-8 PMID: 7815542
  46. Hepatitis C virus (HCV) genotype distribution in German isolates: studies on the sequence variability in the E2 and NS5 region.
    Arch Virol. 1994;139(3-4):379-88 PMID: 7832643
  47. The origin of hepatitis C virus genotypes.
    J Gen Virol. 1997 Feb;78 ( Pt 2):321-8 PMID: 9018053
  48. Variation of the hepatitis C virus 5' non-coding region: implications for secondary structure, virus detection and typing. The International HCV Collaborative Study Group.
    J Gen Virol. 1995 Jul;76 ( Pt 7):1749-61 PMID: 9049380
  49. Epitope mapping of antibodies directed against hypervariable region 1 in acute self-limiting and chronic infections due to hepatitis C virus.
    J Virol. 1997 May;71(5):4123-7 PMID: 9094694
  50. Virus 'quasispecies': making a mountain out of a molehill?
    J Gen Virol. 1997 Jul;78 ( Pt 7):1511-9 PMID: 9225023
  51. Characteristics of nucleotide substitution in the hepatitis C virus genome: constraints on sequence change in coding regions at both ends of the genome.
    J Mol Evol. 1997 Sep;45(3):238-46 PMID: 9302317
  52. Hepatitis C viral complexity detected by single-strand conformation polymorphism and response to interferon therapy.
    Gastroenterology. 1995 Mar;108(3):789-95 PMID: 7533113
Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/JVI.72.6.4893-4905.1998
Published
1998-06-00
Pages
4893-905
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC110045
Subset
IM
Grants
Wellcome Trust · United Kingdom
Databases
GENBANK
AF056733, AF056734, AF056735, AF056736, AF056737, AF056738, AF056739, AF056740, AF056741, AF056742, AF056743, AF056744, AF056745, AF056746, AF056747, AF056748, AF056749, AF056750, AF056751, AF056752, AF056753, AF056754, AF056755, AF056756, AF056757, AF056758, AF056759, AF056760, AF056761, AF056762
External Links
PubMed source DOI: 10.1128/JVI.72.6.4893-4905.1998 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2