Skip directly to site content Skip directly to page options Skip directly to A-Z link Skip directly to A-Z link Skip directly to A-Z link
Volume 12, Number 2—February 2006
Perspective

Detecting Hepatitis B Surface Antigen Mutants

Paul F. Coleman*Comments to Author 
Author affiliation: *Abbott Laboratories, Abbott Park, Illinois, USA

Main Article

Table 1

Detection of most common hepatitis B surface antigen (HBsAg) mutants by 9 commercial assays (29)*†

Assay configuration Ausria poly/poly Auszyme mono/mono IMx HBsAg mono/poly AxSYM HBsAg mono/poly PRISM HBsAg mono/poly ARCHITECT HBsAg mono/poly Commercial assay A mono/mono Commercial assay B mono/mono Commercial assay C poly/mono
HBsAg mutants
Wildtype + + + + + + + + + + + + + + + + + +
Thr126- Ser + + + + + + + + + + + + + + +
Gln129- His + + + + + + + + + + + + + + +
Met133- Leu + + + + + + + + + + + + + + + + + +
Asp144- Ala + + + + + + + + + + + + – + + + +
Gly145- Arg + + + + + + + + + + + + – – –
Thr126- Ser + Gly145- Arg + + + + + + + + + + + – – –
Pro142- Leu + Gly145- Arg + + + + + + + + + + + + – – –
Pro142- Ser + Gly145- Arg + + + + + + + + + + + + – – –
Asp144- Ala + Gly145- Arg + + + + + + + + + + + – – –

*All positive samples confirmed in their respective assays.
†+ +, equivalent detection to wild-type antigen; +, detection less than wild-type antigen; –, not detected.

Main Article

References
  1. Kao  JH, Chen  DS. Global control of hepatitis B virus. Lancet Infect Dis. 2002;2:395–403. DOIPubMedGoogle Scholar
  2. Esteban  J, Martell  M, Carman  WF, Gomez  J, Esteban  J, Martell  M, The impact of rapid evolution of the hepatitis viruses. In: Domingo E, Webster RG, Holland JI, editors. Origin and evolution of viruses. London: Academic Press; 1999. p. 345–65.
  3. Norder  H, Couroucé  A, Coursaget  P, Echevarria  J, Lee  S, Mushahwar  I, Genetic diversity of hepatitis B virus strains derived worldwide: genotypes, subgenotypes, and HBsAg subtypes. Intervirology. 2004;47:289–309. DOIPubMedGoogle Scholar
  4. Ngui  S, Hallet  R, Teo  C. Natural and iatrogenic variation in hepatitis B virus. Rev Med Virol. 1999;9:183–209. DOIPubMedGoogle Scholar
  5. Weinberger  K, Bauer  T, Bohm  S, Jilg  W. High genetic variability of the group-specific a-determinant of hepatitis B virus surface antigen (HBsAg) and the corresponding fragment of the viral polymerase in chronic virus carriers lacking detectable HBsAg in serum. J Gen Virol. 2000;81:1165–74.PubMedGoogle Scholar
  6. Locarnini  S. Hepatitis B viral resistance: mechanisms and diagnosis. J Hepatol. 2003;39:Suppl S124–32.
  7. Nainan  O, Khristova  M, Byun  K, Xia  G, Taylor  P, Stevens  C, Genetic variation of hepatitis B surface antigen coding region among infants with chronic hepatitis B virus infection. J Med Virol. 2002;68:319–27. DOIPubMedGoogle Scholar
  8. Mangold  C, Streeck  R. Mutational analysis of the cysteine residues in the hepatitis B virus small envelope protein. J Virol. 1993;67:4588–97.PubMedGoogle Scholar
  9. Khan  N, Guarnieri  M, Ahn  S, Jisu  Li, Zhou  Y, Bang  G, Modulation of hepatitis B virus secretion by naturally occurring mutations in the S gene. J Virol. 2004;78:3262–70. DOIPubMedGoogle Scholar
  10. Qiu  X, Schroeder  P, Bridon  D. Identification and characterization of a C(K/R)TC motif as a common epitope present in all subtypes of hepatitis B surface antigen. J Immunol. 1996;156:3350–6.PubMedGoogle Scholar
  11. Chen  Y-C, Delbrook  K, Dealwis  C, Mimms  L, Mushahwar  I, Mandecki  W. Discontinuous epitopes of hepatitis B surface antigen derived from a filamentous phage peptide library. Proc Natl Acad Sci U S A. 1996;93:1997–2001. DOIPubMedGoogle Scholar
  12. Antoni  BA, Rodriguez-Crespo  I, Gomez-Gutierrez  J, Nieto  M, Peterson  D, Gavilanes  F. Site-directed mutagenesis of cysteine residues of hepatitis B surface antigen. Eur J Biochem. 1994;222:121–7. DOIPubMedGoogle Scholar
  13. Maillard  P, Pillot  J. At least three epitopes are recognized by the human repertoire in the hepatitis B virus group a antigen inducing protection; possible consequences for seroprevention and serodiagnosis. Res Virol. 1998;149:153–61. DOIPubMedGoogle Scholar
  14. Shearera  M, Sureaub  C, Dunbarc  B, Kennedy  R. Structural characterization of viral neutralizing monoclonal antibodies to hepatitis B surface antigen. Mol Immunol. 1998;35:1149–60. DOIPubMedGoogle Scholar
  15. Jolivet-Reynaud  C, Lesenchal  M, O'Donnell  B, Becquant  L, Foussadiez  A, Forge  F, Localization of hepatitis B surface antigen epitopes present on variants and specifically recognized by anti-hepatitis B surface antigen monoclonal antibodies. J Med Virol. 2001;65:241–9. DOIPubMedGoogle Scholar
  16. Zanetti  A, Tanzi  E, Manzillo  G, Maio  G, Sbreglia  C, Caporaso  N, Hepatitis B variant in Europe. Lancet. 1988;2:1132–3. DOIPubMedGoogle Scholar
  17. Carman  W, Zanetti  A, Karayiannis  P, Waters  J, Manzillo  G, Tanzi  E, Vaccine-induced escape mutant of hepatitis B virus. Lancet. 1990;336:325–9. DOIPubMedGoogle Scholar
  18. Shizuma  T, Hasegawa  K, Ishikawa  K, Naritomi  T, Iizuka  A, Kanai  N, Molecular analysis of antigenicity and immunogenicity of a vaccine-induced escape mutant of hepatitis B virus. J Gastroenterol. 2003;38:244–53. DOIPubMedGoogle Scholar
  19. Ogata  N, Zanetti  AR, Yu  M, Miller  RH, Purcell  RH. Infectivity and pathogenicity in chimpanzees of a surface gene mutant of hepatitis B virus that emerged in a vaccinated infant. J Infect Dis. 1997;175:511–23. DOIPubMedGoogle Scholar
  20. Ogata  N, Cote  PJ, Zanetti  AR, Miller  RH, Shapiro  M, Gerin  J, Licensed recombinant hepatitis B vaccines protect chimpanzees against infection with the prototype surface gene mutant of hepatitis B virus. Hepatology. 1999;30:779–86. DOIPubMedGoogle Scholar
  21. Wilson  J, Nokes  D, Carman  W. Predictions of the emergence of vaccine-resistant hepatitis B in The Gambia using a mathematical model. Epidemiol Infect. 2000;124:295–307. DOIPubMedGoogle Scholar
  22. Zuckerman  J, Zuckerman  A. Mutations of the surface protein of hepatitis B virus. Antiviral Res. 2003;60:75–8. DOIPubMedGoogle Scholar
  23. Carman  W. The clinical significance of surface antigen variants of hepatitis B virus. J Viral Hepat. 1997;4:11–20. DOIPubMedGoogle Scholar
  24. Yamamoto  K, Horikita  M, Tsuda  F, Itoh  K, Akahane  Y, Yotsumoto  S, Naturally occurring escape mutants of hepatitis B virus with various mutations in the S gene in carriers seropositive of antibody to hepatitis B surface antigen. J Virol. 1994;68:2671–6.PubMedGoogle Scholar
  25. Hou  J, Karayiannis  P, Waters  J, Lou  K, Liang  C, Thomas  H. A unique insertion in the S gene of surface antigen-negative hepatitis B virus Chinese carriers. Hepatology. 1995;21:273–8.PubMedGoogle Scholar
  26. Weinberger  K, Zoulek  G, Bauer  T, Bohm  S, Jilg  W. A novel deletion mutant of hepatitis B virus surface antigen. J Med Virol. 1999;58:105–10. DOIPubMedGoogle Scholar
  27. Gunther  S, Sommer  G, von Breunig  F, Iwanska  A, Kalinina  T, Sterneck  M, Amplification of full-length hepatitis B virus genomes from samples from patients with low levels of viremia: frequency and functional consequences of PCR-introduced mutations. J Clin Microbiol. 1998;36:531–8.PubMedGoogle Scholar
  28. Carman  W, van Deursen  F, Mimms  L, Hardie  D, Coppola  R, Decker  R, The prevalence of surface antigen variants of hepatitis B virus in Papua New Guinea, South Africa, and Sardinia. Hepatology. 1997;26:1658–66. DOIPubMedGoogle Scholar
  29. Coleman  P, Chen  Y-C, Mushahwar  IK. Immunoassay detection of hepatitis B surface antigen mutants. J Med Virol. 1999;59:19–24. DOIPubMedGoogle Scholar
  30. Ireland  J, O'Donnell  B, Basuni  A, Kean  J, Wallace  L, Lau  G, Reactivity of 13 in vitro expressed hepatitis B surface antigen variants in 7 commercial diagnostic assays. Hepatology. 2000;31:1176–82. DOIPubMedGoogle Scholar
  31. Moerman  B, Moons  V, Sommer  H, Schmitt  Y, Stetter  M. Evaluation of sensitivity for wild-type and mutant forms of hepatitis B surface antigen by four commercial HBsAg assays. Clin Lab. 2004;50:159–62.PubMedGoogle Scholar
  32. Zaaijer  HL, Vrielink  H, Koot  M. Early detection of hepatitis B surface antigen and detection of HBsAg mutants: a comparison of five assays. Vox Sang. 2001;81:219–21. DOIPubMedGoogle Scholar
  33. Levicnik-Stezinar  S. Hepatitis B surface antigen escape mutant in a first time blood donor potentially missed by a routine screening assay. Clin Lab. 2004;50:49–51.PubMedGoogle Scholar
  34. Koyanagi  T, Nakamuta  M, Sakai  H, Sugimoto  R, Enjoji  M, Koto  K, Analysis of HBs antigen negative variant of hepatitis B virus: unique substitutions, Glu129 to Asp and Gly145 to Ala in the surface antigen gene. Med Sci Monit. 2000;6:1165–9.PubMedGoogle Scholar
  35. Tallo  T, Norder  H, Tefanova  V, Krispin  T, Priimagi  L, Mukomolov  S, Hepatitis B virus genotype D strains from Estonia share sequence similarity with strains from Siberia and may specify ayw4. J Med Virol. 2004;74:221–7. DOIPubMedGoogle Scholar
  36. Gerlich  W. Diagnostic problems caused by HBsAg mutants—a consensus report of an expert meeting. Intervirology. 2004;47:310–3. DOIPubMedGoogle Scholar
  37. Oon  C, Lim  G, Ye  Z, Goh  K, Tan  K, Yo  S, Molecular epidemiology of hepatitis B virus vaccine variants in Singapore. Vaccine. 1995;13:699–702. DOIPubMedGoogle Scholar
  38. Hsu  HY, Chang  MH, Liaw  SH, Ni  YH, Chen  HL. Changes of hepatitis B surface antigen variants in carrier children before and after universal vaccination in Taiwan. Hepatology. 1999;30:1312–7. DOIPubMedGoogle Scholar
  39. Thakur  V,1 Kazim  S, Guptan  R,1 Hasnain  S, Bartholomeusz  A, Malhotra  V, Transmission of G145R mutant of HBV to an unrelated contact. J Med Virol. 2005;76:40–6. DOIPubMedGoogle Scholar
  40. Torresi  J, Earnest-Silveira  L, Civitico  G, Walters  TE, Lewin  SR, Fyfe  J, Restoration of replication phenotype of lamivudine-resistant hepatitis B virus mutants by compensatory changes in the "fingers" subdomain of the viral polymerase selected as a consequence of mutations in the overlapping S gene. Virology. 2002;299:88–99. DOIPubMedGoogle Scholar

Main Article

Page created: February 02, 2012
Page updated: February 02, 2012
Page reviewed: February 02, 2012
The conclusions, findings, and opinions expressed by authors contributing to this journal do not necessarily reflect the official position of the U.S. Department of Health and Human Services, the Public Health Service, the Centers for Disease Control and Prevention, or the authors' affiliated institutions. Use of trade names is for identification only and does not imply endorsement by any of the groups named above.
file_external