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Proc Natl Acad Sci U S A. Apr 15, 1992; 89(8): 3468–3472.
PMCID: PMC48889

Evidence for immune selection of hepatitis C virus (HCV) putative envelope glycoprotein variants: potential role in chronic HCV infections.

Abstract

E2/nonstructural protein 1, the putative envelope glycoprotein (gp72) of HCV, possesses an N-terminal hypervariable (E2 HV) domain from amino acids 384 to 414 of unknown significance. The high degree of amino acid sequence variation in the E2 HV domain appears to be comparable to that observed in the human immunodeficiency virus type 1 gp120 V3 domain. This observation and the observation that the HCV E2 HV domain lacks conserved secondary structure imply that, like the V3 loop of human immunodeficiency virus 1 gp120, the N-terminal E2 region may encode protective epitopes that are subject to immune selection. Antibody-epitope binding studies revealed five isolate-specific linear epitopes located in the E2 HV region. These results suggest that the E2 HV domain is a target for the human immune response and that, in addition to the three major groups of HCV, defined by nucleotide and amino acid sequence identity among HCV isolates, E2 HV-specific subgroups also exist. Analysis of the partial or complete E2 sequences of two individuals indicated that E2 HV variants can either coexist simultaneously in a single individual or that a particular variant may predominate during different episodes of disease. In the latter situation, we found one individual who developed antibodies to a subregion of the E2 HV domain (amino acids 396-407) specific to a variant that was predominant during one major episode of hepatitis but who lacked detectable antibodies to the corresponding region of a second variant that was predominant during a later episode of disease. The data suggest that the variability in the E2 HV domain may result from immune selection. The findings of this report could impact vaccine strategies and drug therapy programs designed to control and eliminate HCV.

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  • Choo QL, Kuo G, Weiner AJ, Overby LR, Bradley DW, Houghton M. Isolation of a cDNA clone derived from a blood-borne non-A, non-B viral hepatitis genome. Science. 1989 Apr 21;244(4902):359–362. [PubMed]
  • Kuo G, Choo QL, Alter HJ, Gitnick GL, Redeker AG, Purcell RH, Miyamura T, Dienstag JL, Alter MJ, Stevens CE, et al. An assay for circulating antibodies to a major etiologic virus of human non-A, non-B hepatitis. Science. 1989 Apr 21;244(4902):362–364. [PubMed]
  • Choo QL, Weiner AJ, Overby LR, Kuo G, Houghton M, Bradley DW. Hepatitis C virus: the major causative agent of viral non-A, non-B hepatitis. Br Med Bull. 1990 Apr;46(2):423–441. [PubMed]
  • Dienstag JL, Alter HJ. Non-A, non-B hepatitis: evolving epidemiologic and clinical perspective. Semin Liver Dis. 1986 Feb;6(1):67–81. [PubMed]
  • Choo QL, Richman KH, Han JH, Berger K, Lee C, Dong C, Gallegos C, Coit D, Medina-Selby R, Barr PJ, et al. Genetic organization and diversity of the hepatitis C virus. Proc Natl Acad Sci U S A. 1991 Mar 15;88(6):2451–2455. [PMC free article] [PubMed]
  • Houghton M, Weiner A, Han J, Kuo G, Choo QL. Molecular biology of the hepatitis C viruses: implications for diagnosis, development and control of viral disease. Hepatology. 1991 Aug;14(2):381–388. [PubMed]
  • Hijikata M, Kato N, Ootsuyama Y, Nakagawa M, Shimotohno K. Gene mapping of the putative structural region of the hepatitis C virus genome by in vitro processing analysis. Proc Natl Acad Sci U S A. 1991 Jul 1;88(13):5547–5551. [PMC free article] [PubMed]
  • Takeuchi K, Kubo Y, Boonmar S, Watanabe Y, Katayama T, Choo QL, Kuo G, Houghton M, Saito I, Miyamura T. The putative nucleocapsid and envelope protein genes of hepatitis C virus determined by comparison of the nucleotide sequences of two isolates derived from an experimentally infected chimpanzee and healthy human carriers. J Gen Virol. 1990 Dec;71(Pt 12):3027–3033. [PubMed]
  • Han JH, Shyamala V, Richman KH, Brauer MJ, Irvine B, Urdea MS, Tekamp-Olson P, Kuo G, Choo QL, Houghton M. Characterization of the terminal regions of hepatitis C viral RNA: identification of conserved sequences in the 5' untranslated region and poly(A) tails at the 3' end. Proc Natl Acad Sci U S A. 1991 Mar 1;88(5):1711–1715. [PMC free article] [PubMed]
  • Miller RH, Purcell RH. Hepatitis C virus shares amino acid sequence similarity with pestiviruses and flaviviruses as well as members of two plant virus supergroups. Proc Natl Acad Sci U S A. 1990 Mar;87(6):2057–2061. [PMC free article] [PubMed]
  • Montelaro RC, Parekh B, Orrego A, Issel CJ. Antigenic variation during persistent infection by equine infectious anemia virus, a retrovirus. J Biol Chem. 1984 Aug 25;259(16):10539–10544. [PubMed]
  • Rümenapf T, Stark R, Meyers G, Thiel HJ. Structural proteins of hog cholera virus expressed by vaccinia virus: further characterization and induction of protective immunity. J Virol. 1991 Feb;65(2):589–597. [PMC free article] [PubMed]
  • Schlesinger JJ, Brandriss MW, Cropp CB, Monath TP. Protection against yellow fever in monkeys by immunization with yellow fever virus nonstructural protein NS1. J Virol. 1986 Dec;60(3):1153–1155. [PMC free article] [PubMed]
  • Weiner AJ, Brauer MJ, Rosenblatt J, Richman KH, Tung J, Crawford K, Bonino F, Saracco G, Choo QL, Houghton M, et al. 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):842–848. [PubMed]
  • Hijikata M, Kato N, Ootsuyama Y, Nakagawa M, Ohkoshi S, Shimotohno K. Hypervariable regions in the putative glycoprotein of hepatitis C virus. Biochem Biophys Res Commun. 1991 Feb 28;175(1):220–228. [PubMed]
  • Bayer R. Ethical and social policy issues raised by HIV screening: the epidemic evolves and so do the challenges. AIDS. 1989 Mar;3(3):119–124. [PubMed]
  • Kubo Y, Takeuchi K, Boonmar S, Katayama T, Choo QL, Kuo G, Weiner AJ, Bradley DW, Houghton M, Saito I, et al. A cDNA fragment of hepatitis C virus isolated from an implicated donor of post-transfusion non-A, non-B hepatitis in Japan. Nucleic Acids Res. 1989 Dec 25;17(24):10367–10372. [PMC free article] [PubMed]
  • Chomczynski P, Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. [PubMed]
  • Erlich HA, Gelfand D, Sninsky JJ. Recent advances in the polymerase chain reaction. Science. 1991 Jun 21;252(5013):1643–1651. [PubMed]
  • Messing J. New M13 vectors for cloning. Methods Enzymol. 1983;101:20–78. [PubMed]
  • Takeuchi K, Boonmar S, Kubo Y, Katayama T, Harada H, Ohbayashi A, Choo QL, Kuo G, Houghton M, Saito I, et al. Hepatitis C viral cDNA clones isolated from a healthy carrier donor implicated in post-transfusion non-A, non-B hepatitis. Gene. 1990 Jul 16;91(2):287–291. [PubMed]
  • Kato N, Hijikata M, Ootsuyama Y, Nakagawa M, Ohkoshi S, Sugimura T, Shimotohno K. Molecular cloning of the human hepatitis C virus genome from Japanese patients with non-A, non-B hepatitis. Proc Natl Acad Sci U S A. 1990 Dec;87(24):9524–9528. [PMC free article] [PubMed]
  • Maeji NJ, Bray AM, Geysen HM. Multi-pin peptide synthesis strategy for T cell determinant analysis. J Immunol Methods. 1990 Nov 6;134(1):23–33. [PubMed]
  • Geysen HM, Meloen RH, Barteling SJ. Use of peptide synthesis to probe viral antigens for epitopes to a resolution of a single amino acid. Proc Natl Acad Sci U S A. 1984 Jul;81(13):3998–4002. [PMC free article] [PubMed]
  • Levitt M, Greer J. Automatic identification of secondary structure in globular proteins. J Mol Biol. 1977 Aug 5;114(2):181–239. [PubMed]
  • Bittle JL, Houghten RA, Alexander H, Shinnick TM, Sutcliffe JG, Lerner RA, Rowlands DJ, Brown F. Protection against foot-and-mouth disease by immunization with a chemically synthesized peptide predicted from the viral nucleotide sequence. Nature. 1982 Jul 1;298(5869):30–33. [PubMed]
  • Modrow S, Hahn BH, Shaw GM, Gallo RC, Wong-Staal F, Wolf H. Computer-assisted analysis of envelope protein sequences of seven human immunodeficiency virus isolates: prediction of antigenic epitopes in conserved and variable regions. J Virol. 1987 Feb;61(2):570–578. [PMC free article] [PubMed]
  • Okamoto H, Okada S, Sugiyama Y, Yotsumoto S, Tanaka T, Yoshizawa H, Tsuda F, Miyakawa Y, Mayumi M. The 5'-terminal sequence of the hepatitis C virus genome. Jpn J Exp Med. 1990 Jun;60(3):167–177. [PubMed]
  • Kremsdorf D, Porchon C, Kim JP, Reyes GR, Bréchot C. Partial nucleotide sequence analysis of a French hepatitis C virus: implications for HCV genetic variability in the E2/NS1 protein. J Gen Virol. 1991 Oct;72(Pt 10):2557–2561. [PubMed]
  • Takamizawa A, Mori C, Fuke I, Manabe S, Murakami S, Fujita J, Onishi E, Andoh T, Yoshida I, Okayama H. Structure and organization of the hepatitis C virus genome isolated from human carriers. J Virol. 1991 Mar;65(3):1105–1113. [PMC free article] [PubMed]
  • LaRosa GJ, Davide JP, Weinhold K, Waterbury JA, Profy AT, Lewis JA, Langlois AJ, Dreesman GR, Boswell RN, Shadduck P, et al. Conserved sequence and structural elements in the HIV-1 principal neutralizing determinant: corrections and clarifications. Science. 1991 Feb 15;251(4995):811–811. [PubMed]
  • Ogata N, Alter HJ, Miller RH, Purcell RH. 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):3392–3396. [PMC free article] [PubMed]

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