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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;2:395403. 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;47:289309. DOIPubMedGoogle Scholar
  4. Ngui  S, Hallet  R, Teo  C. Natural and iatrogenic variation in hepatitis B virus. Rev Med Virol. 1999;9:183209. 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;81:116574.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;68:31927. DOIPubMedGoogle Scholar
  8. Mangold  C, Streeck  R. Mutational analysis of the cysteine residues in the hepatitis B virus small envelope protein. J Virol. 1993;67:458897.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;78:326270. 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;156:33506.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;93:19972001. 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;222:1217. 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;149:15361. 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;35:114960. 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;65:2419. DOIPubMedGoogle Scholar
  16. Zanetti  A, Tanzi  E, Manzillo  G, Maio  G, Sbreglia  C, Caporaso  N, Hepatitis B variant in Europe. Lancet. 1988;2:11323. 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;336:3259. 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;38:24453. 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;175:51123. 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;30:77986. 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;124:295307. DOIPubMedGoogle Scholar
  22. Zuckerman  J, Zuckerman  A. Mutations of the surface protein of hepatitis B virus. Antiviral Res. 2003;60:758. DOIPubMedGoogle Scholar
  23. Carman  W. The clinical significance of surface antigen variants of hepatitis B virus. J Viral Hepat. 1997;4:1120. 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;68:26716.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;21:2738.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;58:10510. 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;36:5318.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;26:165866. DOIPubMedGoogle Scholar
  29. Coleman  P, Chen  Y-C, Mushahwar  IK. Immunoassay detection of hepatitis B surface antigen mutants. J Med Virol. 1999;59:1924. 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;31:117682. 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;50:15962.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;81:21921. 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;50:4951.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;6:11659.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;74:2217. DOIPubMedGoogle Scholar
  36. Gerlich  W. Diagnostic problems caused by HBsAg mutants—a consensus report of an expert meeting. Intervirology. 2004;47:3103. 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;13:699702. 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;30:13127. 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;76:406. 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;299:8899. DOIPubMedGoogle Scholar

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Page created: February 02, 2012
Page updated: February 02, 2012
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