Skip to main content
PMC home page
Journal of Virology logoLink to Journal of Virology
. 1997 May;71(5):4123–4127. doi: 10.1128/jvi.71.5.4123-4127.1997

Epitope mapping of antibodies directed against hypervariable region 1 in acute self-limiting and chronic infections due to hepatitis C virus.

A Zibert 1, W Kraas 1, H Meisel 1, G Jung 1, M Roggendorf 1
PMCID: PMC191569  PMID: 9094694

Abstract

Epitopes of hypervariable region 1 (HVR1) were mapped by enzyme-linked immunosorbent assay using follow-up sera of patients, all of whom were infected with the same isolate of hepatitis C virus (HCV). Our results suggest that (i) an early appearance (up to month 13 postinfection) of antibodies directed to the N terminus of HVR1 is associated with acute self-limiting infections of HCV and (ii) isolate-independent antibodies which are mainly directed to the C terminus of HVR1 seem to persist in chronically infected patients. The relevance of HVR1-specific antibodies for neutralization was evaluated by characterization of a rabbit serum.

Full Text

The Full Text of this article is available as a PDF (154.1 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Choo Q. L., Kuo G., Ralston R., Weiner A., Chien D., Van Nest G., Han J., Berger K., Thudium K., Kuo C. Vaccination of chimpanzees against infection by the hepatitis C virus. Proc Natl Acad Sci U S A. 1994 Feb 15;91(4):1294–1298. doi: 10.1073/pnas.91.4.1294. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Choo Q. L., Kuo G., Weiner A. J., Overby L. R., Bradley D. W., 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. doi: 10.1126/science.2523562. [DOI] [PubMed] [Google Scholar]
  3. Diepolder H. M., Zachoval R., Hoffmann R. M., Wierenga E. A., Santantonio T., Jung M. C., Eichenlaub D., Pape G. R. Possible mechanism involving T-lymphocyte response to non-structural protein 3 in viral clearance in acute hepatitis C virus infection. Lancet. 1995 Oct 14;346(8981):1006–1007. doi: 10.1016/s0140-6736(95)91691-1. [DOI] [PubMed] [Google Scholar]
  4. Dittmann S., Roggendorf M., Dürkop J., Wiese M., Lorbeer B., Deinhardt F. Long-term persistence of hepatitis C virus antibodies in a single source outbreak. J Hepatol. 1991 Nov;13(3):323–327. doi: 10.1016/0168-8278(91)90076-n. [DOI] [PubMed] [Google Scholar]
  5. Driesel G., Wirth D., Stark K., Baumgarten R., Sucker U., Schreier E. 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):379–388. doi: 10.1007/BF01310799. [DOI] [PubMed] [Google Scholar]
  6. Duvoux C., Pawlotsky J. M., Cherqui D., Tran van Nhieu J., Metreau J. M., Fagniez P. L., Duval J., Zafrani E. S., Dhumeaux D. Serial quantitative determination of hepatitis C virus RNA levels after liver transplantation. A useful test for diagnosis of hepatitis C virus reinfection. Transplantation. 1995 Sep 15;60(5):457–461. doi: 10.1097/00007890-199509000-00009. [DOI] [PubMed] [Google Scholar]
  7. Farci P., Alter H. J., Govindarajan S., Wong D. C., Engle R., Lesniewski R. R., Mushahwar I. K., Desai S. M., Miller R. H., Ogata N. Lack of protective immunity against reinfection with hepatitis C virus. Science. 1992 Oct 2;258(5079):135–140. doi: 10.1126/science.1279801. [DOI] [PubMed] [Google Scholar]
  8. Farci P., Alter H. J., Wong D. C., Miller R. H., Govindarajan S., Engle R., Shapiro M., Purcell R. H. Prevention of hepatitis C virus infection in chimpanzees after antibody-mediated in vitro neutralization. Proc Natl Acad Sci U S A. 1994 Aug 2;91(16):7792–7796. doi: 10.1073/pnas.91.16.7792. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Higashi Y., Kakumu S., Yoshioka K., Wakita T., Mizokami M., Ohba K., Ito Y., Ishikawa T., Takayanagi M., Nagai Y. Dynamics of genome change in the E2/NS1 region of hepatitis C virus in vivo. Virology. 1993 Dec;197(2):659–668. doi: 10.1006/viro.1993.1641. [DOI] [PubMed] [Google Scholar]
  10. 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. doi: 10.1016/s0006-291x(05)81223-9. [DOI] [PubMed] [Google Scholar]
  11. Höhne M., Schreier E., Roggendorf M. 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. doi: 10.1007/BF01311170. [DOI] [PubMed] [Google Scholar]
  12. Kato N., Ootsuyama Y., Sekiya H., Ohkoshi S., Nakazawa T., Hijikata M., Shimotohno K. Genetic drift in hypervariable region 1 of the viral genome in persistent hepatitis C virus infection. J Virol. 1994 Aug;68(8):4776–4784. doi: 10.1128/jvi.68.8.4776-4784.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Kato N., Ootsuyama Y., Tanaka T., Nakagawa M., Nakazawa T., Muraiso K., Ohkoshi S., Hijikata M., Shimotohno K. Marked sequence diversity in the putative envelope proteins of hepatitis C viruses. Virus Res. 1992 Feb;22(2):107–123. doi: 10.1016/0168-1702(92)90038-b. [DOI] [PubMed] [Google Scholar]
  14. Kato N., Sekiya H., Ootsuyama Y., Nakazawa T., Hijikata M., Ohkoshi S., Shimotohno K. Humoral immune response to hypervariable region 1 of the putative envelope glycoprotein (gp70) of hepatitis C virus. J Virol. 1993 Jul;67(7):3923–3930. doi: 10.1128/jvi.67.7.3923-3930.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Kojima M., Osuga T., Tsuda F., Tanaka T., Okamoto H. Influence of antibodies to the hypervariable region of E2/NS1 glycoprotein on the selective replication of hepatitis C virus in chimpanzees. Virology. 1994 Nov 1;204(2):665–672. doi: 10.1006/viro.1994.1582. [DOI] [PubMed] [Google Scholar]
  16. Kurosaki M., Enomoto N., Marumo F., Sato C. Evolution and selection of hepatitis C virus variants in patients with chronic hepatitis C. Virology. 1994 Nov 15;205(1):161–169. doi: 10.1006/viro.1994.1631. [DOI] [PubMed] [Google Scholar]
  17. Lai M. E., Mazzoleni A. P., Argiolu F., De Virgilis S., Balestrieri A., Purcell R. H., Cao A., Farci P. Hepatitis C virus in multiple episodes of acute hepatitis in polytransfused thalassaemic children. Lancet. 1994 Feb 12;343(8894):388–390. doi: 10.1016/s0140-6736(94)91224-6. [DOI] [PubMed] [Google Scholar]
  18. Laskus T., Wang L. F., Rakela J., Vargas H., Pinna A. D., Tsamandas A. C., Demetris A. J., Fung J. Dynamic behavior of hepatitis C virus in chronically infected patients receiving liver graft from infected donors. Virology. 1996 Jun 1;220(1):171–176. doi: 10.1006/viro.1996.0297. [DOI] [PubMed] [Google Scholar]
  19. Martell M., Esteban J. I., Quer J., Genescà J., Weiner A., Esteban R., Guardia J., Gómez J. Hepatitis C virus (HCV) circulates as a population of different but closely related genomes: quasispecies nature of HCV genome distribution. J Virol. 1992 May;66(5):3225–3229. doi: 10.1128/jvi.66.5.3225-3229.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Rosa D., Campagnoli S., Moretto C., Guenzi E., Cousens L., Chin M., Dong C., Weiner A. J., Lau J. Y., Choo Q. L. A quantitative test to estimate neutralizing antibodies to the hepatitis C virus: cytofluorimetric assessment of envelope glycoprotein 2 binding to target cells. Proc Natl Acad Sci U S A. 1996 Mar 5;93(5):1759–1763. doi: 10.1073/pnas.93.5.1759. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Scarselli E., Cerino A., Esposito G., Silini E., Mondelli M. U., Traboni C. 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):4407–4412. doi: 10.1128/jvi.69.7.4407-4412.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Shimizu Y. K., Hijikata M., Iwamoto A., Alter H. J., Purcell R. H., Yoshikura H. Neutralizing antibodies against hepatitis C virus and the emergence of neutralization escape mutant viruses. J Virol. 1994 Mar;68(3):1494–1500. doi: 10.1128/jvi.68.3.1494-1500.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Taniguchi S., Okamoto H., Sakamoto M., Kojima M., Tsuda F., Tanaka T., Munekata E., Muchmore E. E., Peterson D. A., Mishiro S. 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. doi: 10.1006/viro.1993.1378. [DOI] [PubMed] [Google Scholar]
  24. Weiner A. J., Brauer M. J., Rosenblatt J., Richman K. H., Tung J., Crawford K., Bonino F., Saracco G., Choo Q. L., Houghton M. 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. doi: 10.1016/0042-6822(91)90104-j. [DOI] [PubMed] [Google Scholar]
  25. Weiner A. J., Geysen H. M., Christopherson C., Hall J. E., Mason T. J., Saracco G., Bonino F., Crawford K., Marion C. D., Crawford K. A. 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):3468–3472. doi: 10.1073/pnas.89.8.3468. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Weiner A., Erickson A. L., Kansopon J., Crawford K., Muchmore E., Hughes A. L., Houghton M., Walker C. M. Persistent hepatitis C virus infection in a chimpanzee is associated with emergence of a cytotoxic T lymphocyte escape variant. Proc Natl Acad Sci U S A. 1995 Mar 28;92(7):2755–2759. doi: 10.1073/pnas.92.7.2755. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Zibert A., Schreier E., Roggendorf M. Antibodies in human sera specific to hypervariable region 1 of hepatitis C virus can block viral attachment. Virology. 1995 Apr 20;208(2):653–661. doi: 10.1006/viro.1995.1196. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Virology are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES