Search tips
Search criteria 


Logo of jvirolPermissionsJournals.ASM.orgJournalJV ArticleJournal InfoAuthorsReviewers
J Virol. 1994 March; 68(3): 1494–1500.
PMCID: PMC236605

Neutralizing antibodies against hepatitis C virus and the emergence of neutralization escape mutant viruses.


We developed an in vitro assay for antibodies to hepatitis C virus (HCV) that bind to virions and prevent initiation of the replication cycle in susceptible cells in vitro. These antibodies therefore appear to be capable of neutralizing the virus. Using this assay and a standard inoculum of HCV of known infectivity, we have measured the antibody in serial serum samples obtained from the same chronically infected patient over 14 years following onset of his hepatitis. Such antibody was found in sera collected within 5 years of onset of hepatitis but not in later sera. In double immunoprecipitation experiments with anti-human immunoglobulin, the same sera that contained neutralizing antibody were found to contain antibody that bound to HCV to form antigen-antibody complexes immunoprecipitable with anti-human globulin. Similarly, plasma collected from this patient in 1990, 13 years after onset of hepatitis, and which contained HCV that had diverged genetically from the 1977 strain, did not contain antibody capable of neutralizing either the 1977 or the 1990 strain of HCV. However, plasma collected a year later (1991, 14 years after onset of hepatitis) contained neutralizing antibody to the 1990, but not the 1977, strain of HCV. These results suggest that HCV does induce antivirion antibody, as measured by blocking of initiation of the replication cycle of virus in cells and by the formation of immunoprecipitable antigen-antibody complexes but that these antibodies are isolate specific and change over time. Thus, these antivirion antibodies function as neutralizing antibodies and are probably in vitro correlates of the attempt of the host to contain the emergence of neutralization-resistant variants of HCV over time.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.5M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Bukh J, Purcell RH, Miller RH. Sequence analysis of the 5' noncoding region of hepatitis C virus. Proc Natl Acad Sci U S A. 1992 Jun 1;89(11):4942–4946. [PubMed]
  • Farci P, Alter HJ, Govindarajan S, Wong DC, Engle R, Lesniewski RR, Mushahwar IK, Desai SM, Miller RH, Ogata N, et al. Lack of protective immunity against reinfection with hepatitis C virus. Science. 1992 Oct 2;258(5079):135–140. [PubMed]
  • Farci P, Alter HJ, Wong D, Miller RH, Shih JW, Jett B, Purcell RH. A long-term study of hepatitis C virus replication in non-A, non-B hepatitis. N Engl J Med. 1991 Jul 11;325(2):98–104. [PubMed]
  • Feinstone SM, Alter HJ, Dienes HP, Shimizu Y, Popper H, Blackmore D, Sly D, London WT, Purcell RH. Non-A, non-B hepatitis in chimpanzees and marmosets. J Infect Dis. 1981 Dec;144(6):588–598. [PubMed]
  • Gilliam JH, 3rd, Geisinger KR, Richter JE. Primary hepatocellular carcinoma after chronic non-A, non-B post-transfusion hepatitis. Ann Intern Med. 1984 Dec;101(6):794–795. [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]
  • Hijikata M, Shimizu YK, Kato H, Iwamoto A, Shih JW, Alter HJ, Purcell RH, Yoshikura H. Equilibrium centrifugation studies of hepatitis C virus: evidence for circulating immune complexes. J Virol. 1993 Apr;67(4):1953–1958. [PMC free article] [PubMed]
  • Kato N, Ootsuyama Y, Ohkoshi S, Nakazawa T, Sekiya H, Hijikata M, Shimotohno K. Characterization of hypervariable regions in the putative envelope protein of hepatitis C virus. Biochem Biophys Res Commun. 1992 Nov 30;189(1):119–127. [PubMed]
  • 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. [PMC free article] [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. [PubMed]
  • Shimizu YK, Iwamoto A, Hijikata M, Purcell RH, Yoshikura H. Evidence for in vitro replication of hepatitis C virus genome in a human T-cell line. Proc Natl Acad Sci U S A. 1992 Jun 15;89(12):5477–5481. [PubMed]
  • Shimizu YK, Purcell RH, Yoshikura H. Correlation between the infectivity of hepatitis C virus in vivo and its infectivity in vitro. Proc Natl Acad Sci U S A. 1993 Jul 1;90(13):6037–6041. [PubMed]
  • Tanaka E, Kiyosawa K, Nakatsuji Y, Inoue Y, Miyamura T, Chiba J, Furuta S. Clinical significance of antibodies to nonstructural and core proteins of hepatitis C virus in posttransfusion hepatitis patients during long-term follow-up. J Med Virol. 1993 Apr;39(4):318–324. [PubMed]
  • Taniguchi S, Okamoto H, Sakamoto M, Kojima M, Tsuda F, Tanaka T, Munekata E, Muchmore EE, Peterson DA, 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. [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]
  • Weiner AJ, Geysen HM, Christopherson C, Hall JE, Mason TJ, Saracco G, Bonino F, Crawford K, Marion CD, Crawford KA, et al. 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. [PubMed]
  • Yoshikura H. Thermostability of human immunodeficiency virus (HIV-1) in a liquid matrix is far higher than that of an ecotropic murine leukemia virus. Jpn J Cancer Res. 1989 Jan;80(1):1–5. [PubMed]

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