Natural and iatrogenic variation in hepatitis B virus

Ngui, Siew Lin; Hallet, R.; Teo, Chong Gee

doi:10.1002/(sici)1099-1654(199907/09)9:3<183::aid-rmv248>3.0.co;2-p

Cited by 41 publications

(22 citation statements)

References 185 publications

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“…Mutations in this region can affect anti-HBsAb binding and cause discrepant reactivity between diagnostic assays that employ different reagent configurations, reducing or abrogating the sensitivity of detection (1,9,11,20,22,28,53). While the glycine-to-arginine G145R substitution is the predominant HBsAg immune escape variant described in the literature (9, 53), a wide range of other mutants have also been described (1,21,27,33,44,49,52). Genotype E shows approximately 8% amino acid divergence from genotype A, which is commonly used as the reference virus type for the development of HBsAg diagnostic assays (35).…”

Section: Discussionmentioning

confidence: 99%

Detection of Highly Prevalent Hepatitis B Virus Coinfection among HIV-Seropositive Persons in Ghana

et al. 2010

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Section: Discussionmentioning

confidence: 99%

Detection of Highly Prevalent Hepatitis B Virus Coinfection among HIV-Seropositive Persons in Ghana

et al. 2010

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“…S-gene mutants have been associated with an aggressive or worsening clinical course (16,20). The matter of whether the current vaccine is effective in preventing infection with these mutants, particularly in infants born to HBV carrier mothers, is under debate (9,11,25,30).…”

Section: Discussionmentioning

confidence: 99%

“…However, this exposure of HBsAg, coupled with the fact that HBV demonstrates a 10-fold-greater mutation rate than other DNA viruses (14), provides an opportunity for the appearance of point mutations, insertions, and deletions in the S gene. Related to the appearance of surface gene variations is the emergence of immune escape variants in individuals who become infected with HBV despite the presence of anti-HBs antibody derived either through vaccination or hepatitis B immunoglobulin (HBIg) prophylaxis (10,17,20). One of the most frequently observed mutations in these variants is a change from glycine to arginine at amino acid 145 (G145R) within the major hydrophilic domain of the S protein (6).…”

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confidence: 99%

Sensitive Detection of HBsAg Mutants by a Gap Ligase Chain Reaction Assay

Osiowy

2002

J Clin Microbiol

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Hepatitis B virus (HBV) surface gene variants have been associated with diagnostic escape and immune escape following vaccination. The most common mutation observed in these variants is a glycine-to-arginine substitution at amino acid 145 (G145R). In order to sensitively detect the presence of this mutant in serum, a new molecular detection system was developed; in this new system, a gap ligase chain reaction (gLCR) assay was coupled with electrochemiluminescence detection of reaction products. The gLCR assay could detect approximately 10 copies of mutant DNA and could discriminate low levels of mutant DNA in the presence of excess wild-type DNA. Detection of the G145R mutant in clinical specimens was evaluated by testing 56 suspect serum specimens. The G145R mutation was observed in 18 of 28 HBV-DNA-positive samples. The approximate percentage of mutant present in each specimen was calculated by comparison with a standard curve of an increasing ratio of mutant DNA to wild-type DNA. Most samples contained a very low percentage of mutant virus (approximately 5%), with an observed range of approximately 3 to 74%. The G145R mutation was most frequently observed in specimens producing a diagnostic anomaly or from transplant patients but was also observed in specimens from vaccinated individuals and specimens in which HBsAg diagnostic escape was suspected. Therefore, the gLCR assay is a sensitive and specific method for detection of G145R mutants, which could be modified to include the detection of other HBV mutants.

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“…This replicating process lacks 3Ј exonuclease proofreading activity, leading to misincorporation of bases. Mutation of HBV occurs at a relatively high frequency, estimated to be 2 ϫ 10 Ϫ5 nts per year (14), compared to 10 Ϫ9 nts per year for most other DNA viruses (13). The high mutation and replication rate results in a viral population containing many variants with single mutations, many of which are capable of producing their own progeny.…”

Section: Discussionmentioning

confidence: 99%

Monitoring the Emergence of Hepatitis B Virus Polymerase Gene Variants during Lamivudine Therapy Using the LightCycler

et al. 2001

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Treatment of chronic hepatitis B virus (HBV) infection with lamivudine is associated with the appearance in the circulation of HBV variants with mutations in the YMDD (tyrosine, methionine, aspartate, aspartate) motif of the polymerase gene. Fluorometric real-time PCR with the LightCycler assay was used for the detection of resistant variants. Differences in the hybridization melting curve kinetics of probes bound to the sequences encoding the wild-type or the mutant YMDD motifs (YIDD or YVDD in which the methionine residue is altered to an isoleucine or a valine, respectively) distinguished the single-base changes responsible for the resistance phenotype. The LightCycler probe hybridization assay was applied to 40 serum specimens from 19 patients, and the results were correlated with the nucleotide sequences determined for the corresponding PCR products. All three variants could be identified in the specimens. PCR clones obtained from four patients early in the course and prior to lamivudine therapy were investigated for the appearance of YIDD and YVDD variants with the LightCycler assay. In one patient, a transient appearance of the YIDD variant was observed 6 weeks into therapy. Subsequently, after 11 months of lamivudine therapy, the YVDD variant emerged in that patient.

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Natural and iatrogenic variation in hepatitis B virus

Cited by 41 publications

References 185 publications

Detection of Highly Prevalent Hepatitis B Virus Coinfection among HIV-Seropositive Persons in Ghana

Detection of Highly Prevalent Hepatitis B Virus Coinfection among HIV-Seropositive Persons in Ghana

Sensitive Detection of HBsAg Mutants by a Gap Ligase Chain Reaction Assay

Monitoring the Emergence of Hepatitis B Virus Polymerase Gene Variants during Lamivudine Therapy Using the LightCycler

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