Prevalence of naturally occurring surface gene variants of hepatitis B virus in nonimmunized surface antigen–negative Chinese carriers

Hou, Jinlin; Wang, Zhanghui; Cheng, Jinjun; Yao, Lin; Lau, George; Sun, Jian; Zhou, Fuyuan; Waters, Jennifer A.; Karayiannis, Peter; Luo, Kun

doi:10.1053/jhep.2001.28708

Cited by 174 publications

(182 citation statements)

References 52 publications

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“…In this study, although the frequently emerged variant G145R was not found, some other variants showing single amino acid substitution patterns of the 'a' determinant, which had been reported previously, were observed [29][30][31]. All isolates showing T123A and M133L substitutions, together with 4 of the T143M isolates, were obtained from isolated anti-HBc samples; while one of the T143M isolates was found in samples with anti-HBc and anti-HBs.…”

Section: Lp V Cp L I Pgs S T T S T Gp Ck Tc T T Paqgtsm Fp S Ccc T Kpsupporting

confidence: 58%

“…While M133L substitution did not show significant alteration, both T123A and T143M mutations demonstrated results that should be taken into account; pattern T123A resided in close proximity to the cysteine residues at 121 and 124, which form disulfide bonds that are important for maintaining the 'a' determinant's conformation [30,33]. This close proximity substitution might cause alteration in the steric hindrance that would disturb the disulfide bonds, and hence might affect HBsAg conformation and its detection.…”

Section: Lp V Cp L I Pgs S T T S T Gp Ck Tc T T Paqgtsm Fp S Ccc T Kpmentioning

confidence: 90%

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Occult hepatitis B in blood donors in Indonesia: altered antigenicity of the hepatitis B virus surface protein

et al. 2010

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Background and aims Occult hepatitis B virus infection (OBI) poses a challenge to the safety of blood donation. The prevalence of OBI is not well documented in Indonesia, although this information in such an endemic country is needed. This study was aimed to evaluate the prevalence of occult hepatitis B in blood donors from two cities of Indonesia, and to study the genetic variation and its effect on the predicted antigenicity of HBsAg. Methods Serum samples of 309 regular blood donors negative for HBsAg were tested for anti-HBs and antiHBc. Hepatitis B virus (HBV) DNA isolated from antiHBc-positive samples were analyzed by polymerase chain reaction, cloned and sequenced. Antigenic properties of identified HBsAg mutants were predicted by calculation of the antigenic index. Results Of the 309 HBsAg-negative samples, anti-HBc was positive in 134 (43.4%) and HBV DNA was detected in 25 (8.1%). Seven of the viremic samples had nucleotide substitutions (A521G, A551T, C582T, and A562G) in the S gene, causing amino acid mutations (T123A, M133L, and T143M) in the 'a' determinant of HBsAg that resulted in changes in the predicted antigenicity. Conclusions OBI was detected in blood donors' samples in Indonesia. Anti-HBc was shown to be a better screening parameter than HBsAg, however, it might result in the loss of donors particularly in endemic countries. HBsAg detection failure in this study might be due to mutations altering the protein antigenicity and/or the low-level carriage of HBV.

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Section: Lp V Cp L I Pgs S T T S T Gp Ck Tc T T Paqgtsm Fp S Ccc T Kpsupporting

confidence: 58%

Section: Lp V Cp L I Pgs S T T S T Gp Ck Tc T T Paqgtsm Fp S Ccc T Kpmentioning

confidence: 90%

Occult hepatitis B in blood donors in Indonesia: altered antigenicity of the hepatitis B virus surface protein

et al. 2010

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“…Substitutions at positions 122 and 160 have been identified in different cases and were found to be associated with immune escape or diagnostic failure. Substitutions at the position 122 occurred in chronically HBV-infected patients that were tested negative for HBsAg (Alexopoulou et al, 2004;Grethe et al, 1998;Hou et al, 2001;Weinberger et al, 2000). Tian et al (2007) further confirmed that the K122I substitution had a major influence on HBsAg antigenicity.…”

Section: Introductionmentioning

confidence: 95%

Biological significance of amino acid substitutions in hepatitis B surface antigen (HBsAg) for glycosylation, secretion, antigenicity and immunogenicity of HBsAg and hepatitis B virus replication

Zhang

Tian

et al. 2009

Journal of General Virology

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Amino acid substitutions of hepatitis B surface antigen (HBsAg) may affect the antigenicity and immunogenicity of HBsAg, leading to immune escape and diagnostic failure. The amino acid positions 122 and 160 are known as determinants for HBsAg subtypes d/y and w/r, respectively. The substitution K122I has been shown to strongly affect HBsAg antigenicity. In this study, we investigated the significance of naturally occurring amino acid substitutions K122I, T123N, A159G and K160N. Both T123N and K160N substitutions resulted in additional N-glycosylated forms of HBsAg, while the other mutations produced more glycosylated HBsAg compared with the wild type (wt). Detection of HBsAg by ELISA and immunofluorescence staining indicated that variant HBsAg (vtHBsAg) with K122I was not recognized by HBsAg immunoassays, while vtHBsAg with T123N, A159G, K160N and A159G/K160N had reduced antigenicity. DNA immunization in BALB/c mice revealed that wtHBsAg and vtHBsAg with T123N and K160N are able to induce antibodies to HBsAg (anti-HBs), whereas K122I and A159G greatly impair the ability of HBsAg to trigger anti-HBs responses. The cellular immune response to the HBsAg aa 29-38 epitope was enhanced by the K160N substitution. Using replication competent clones of hepatitis B virus (HBV), T123N and A159G substitutions were shown to strongly reduce virion assembly. The amino acid substitution K160N appeared to compensate for the negative effect of A159G on virion production. These results reveal complex effects of amino acid substitutions on biochemical properties of HBsAg, on antigenicity and immunogenicity, and on the replication of HBV.

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“…Mutant HBV strains displaying amino-acid substitutions in the region known as the 'a' determinant of HBsAg can modify the antigenicity of the protein and may impair virion secretion and HBsAg formation [Chen et al, 2003;Shizuma et al, 2003;Khan et al, 2004], as well as the detection of the antigen by the routine diagnostic tests (Table I) [Wallace et al, 1994;Carman, 1997;Carman et al, 1997;Ireland et al, 2000;Hou et al, 2001;Allain, 2004]. Such mutants have also been reported in association with escape from vaccineinduced immunity [Oon et al, 1995;Carman, 1997;Ho et al, 1998;Chong-Jin et al, 1999;He et al, 2001;Lee et al, 2001;Seddigh-Tonekaboni et al, 2001] and with failures of therapy with specific immunoglobulin in newborns from carrier women and in liver-transplant recipients [Harrison et al, 1994;Oon et al, 1996Oon et al, , 2002Brind et al, 1997;Carman, 1997;Ngui et al, 1997;Protzer-Knolle et al, 1998;Santantonio et al, 1999;Roznovsky et al, 2000;Liu et al, 2002].…”

Section: Introductionmentioning

confidence: 99%

Frequency of hepatitis B virus ‘a’ determinant variants in unselected Spanish chronic carriers

Avellón

Echevarría

2005

Journal of Medical Virology

101

124

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The prevalence in the population of hepatitis B virus (HBV) surface antigen (HBsAg) variants that may impair diagnosis, or allow the virus to escape vaccine‐induced immunity or passive immunoglobulin therapy is unknown. A genome fragment encoding HBsAg amino acids 112–212 was amplified and sequenced from the sera of 272 unselected DNA‐positive, HBV‐chronic carriers from Spain. The genotype and the HBsAg subtype were predicted from the sequences. Analysis of amino‐acid positions 112–157 revealed single or multiple substitutions in 39% of the carriers studied. Mutations were not detected for residues 121, 135, 137, 139, 140, 141, 142, 146, 147, 148, 149, 151, 152, 153, 155, 156, and 157. Substitutions reported previously to be in association with failures of diagnostic tests or with vaccine or immunoglobulin therapy escape were found in 12.5%, 6.6%, and 9.2% of carriers, respectively. Met133Thr (2.2%); Gln129His, Met133Ile, Phe/Tyr134Asn (1.8%); Phe/Tyr134Leu, Gly145Ala (1.5%), and Pro120Thr (1.1%) were the most frequent. Other substitutions, including Gly145Arg (0.4%), were found at a frequency of less than 1%. Samples containing HBV mutants were tested with three commercial assays for HBsAg screening. Almost all the mutants reacted to the upper cut‐off values of the assays, but six samples with weak reactivity with one or more of the methods were also found. Thus, HBV mutants with a potential impact on clinical and public health issues are moderately frequent among chronic carriers from Spain, although their influence on the performance of diagnostic tests seems to be slight. J. Med. Virol. 78:24–36, 2006. © 2005 Wiley‐Liss, inc.

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Prevalence of naturally occurring surface gene variants of hepatitis B virus in nonimmunized surface antigen–negative Chinese carriers

Cited by 174 publications

References 52 publications

Occult hepatitis B in blood donors in Indonesia: altered antigenicity of the hepatitis B virus surface protein

Occult hepatitis B in blood donors in Indonesia: altered antigenicity of the hepatitis B virus surface protein

Biological significance of amino acid substitutions in hepatitis B surface antigen (HBsAg) for glycosylation, secretion, antigenicity and immunogenicity of HBsAg and hepatitis B virus replication

Frequency of hepatitis B virus ‘a’ determinant variants in unselected Spanish chronic carriers

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