Current aspects of hepatitis B surface antigen mutants in Singapore

Oon, Chong Jin; Chen, W. N.

doi:10.1046/j.1365-2893.1998.0050s2017.x

Cited by 52 publications

(39 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Residues M133 and F134 have high mutation frequencies in adults (Fig. 5C), and such mutations are implicated in the development of hepatocellular carcinoma (20,21). Both of the mutations are located in the first loop of the ␣ determinant (residues 124 to 138).…”

Section: Resultsmentioning

confidence: 99%

Change in Hepatitis B Virus Large Surface Antigen Variant Prevalence 13 Years after Implementation of a Universal Vaccination Program in China

Bian

Shen

et al. 2013

J Virol

View full text Add to dashboard Cite

A nationwide hepatitis B virus (HBV) vaccination program was implemented in China starting in 1992.To study the change in HBV variant prevalence with massive immunization, large HBV surface protein (LHBs) genes from HBV surface antigen (HBsAg)-positive sera were amplified and sequenced. The prevalences of LHBs mutants were compared between the 1992 and 2005 surveys in child and adult groups. The prevalence of "␣" determinant mutants in the children increased from 6.5% in 1992 to 14.8% in 2005, where the G145R mutant occurred most frequently. In contrast, mutation frequencies showed little difference between 1992 (9.4%) and 2005 (9.9%) in adults. Moreover, compared to the 1992 survey, the child group surface (S) protein mutation frequency specifically increased (P ‫؍‬ 0.005) in the 2005 survey, but the pre-S region mutation frequency did not show a significant difference (P > 0.05). However, the mutation frequency in the adult group increased in both the pre-S and S regions. Furthermore, the frequencies of the disease-related pre-S2 deletion and start codon mutations were significantly higher in the adult groups than in the child groups in both the 1992 and 2005 surveys (P < 0.01). Massive immunization enhances the HBV S protein mutation; the prevalence of LHBs mutants, particularly disease-related mutants, tends to increase with patient age. Hepatitis B virus (HBV) infection is a serious public health problem worldwide and a major cause of hepatitis, cirrhosis, and hepatocellular carcinoma (HCC) (1). An estimated 350 million people are living with chronic hepatitis B worldwide (2). In China, a national serosurvey in 1992 revealed that the prevalence of hepatitis B surface antigen (HBsAg) was 9.8% in the general population (3). The most recent national serosurvey, in 2006, demonstrated that the HBsAg carrier rate is 7.2%, and the number of chronic HBV carriers is estimated to be 9.3 million (3, 4).China began infant vaccine injections in national disease surveillance points (DSP) as early as 1986, and the four provinces in the current study were also to perform infant vaccinations at that time (5). In 1992, China formally recommended routine immunization with the hepatitis B virus vaccine for infants. Since then, the massive vaccination program has effectively decreased the risk of HBV infection, and the rate of HBsAg-positive children has significantly declined. Among children Ͻ5 years of age, the prevalence of HBsAg has dramatically decreased from 9.67% (1992) to 0.96% (2006). It is estimated that 80 million children are free from HBV infection due to the vaccination program (3).While universal infantile HBV vaccination is very efficacious, an increase in the mutant prevalence or "vaccine escape mutation" after immunization posed a potential threat to the long-term success of massive vaccination (6-8). Hsu et al. studied the prevalence of HBV variants in children in Taiwan and demonstrated that universal vaccination had accelerated the accumulation of HBsAg "␣" determinant mutants (9). The ␣ determinant is a co...

show abstract

Section: Resultsmentioning

confidence: 99%

Change in Hepatitis B Virus Large Surface Antigen Variant Prevalence 13 Years after Implementation of a Universal Vaccination Program in China

Bian

Shen

et al. 2013

J Virol

View full text Add to dashboard Cite

show abstract

“…In contrast, P120Q/T, P127T, Q129H/R, M133T, and G145R were found only in patients with advanced liver disease. Importantly, M133T and G145R are not only related to immune escape (5) but might also be implicated in the development of HCC (49,54,55). Amino acid changes at positions 120 (P120T/Q) and 129 (Q129H/R) have been detected as vaccine/HBIg escape mutants in newborn babies with HBsAg-positive mothers (56,57) and cause false-negative Ͻ80% of the total viral population).…”

Section: Discussionmentioning

confidence: 99%

Ultradeep Sequencing for Detection of Quasispecies Variants in the Major Hydrophilic Region of Hepatitis B Virus in Indonesian Patients

et al. 2015

View full text Add to dashboard Cite

h Quasispecies of hepatitis B virus (HBV) with variations in the major hydrophilic region (MHR) of the HBV surface antigen (HBsAg) can evolve during infection, allowing HBV to evade neutralizing antibodies. These escape variants may contribute to chronic infections. In this study, we looked for MHR variants in HBV quasispecies using ultradeep sequencing and evaluated the relationship between these variants and clinical manifestations in infected patients. We enrolled 30 Indonesian patients with hepatitis B infection (11 with chronic hepatitis and 19 with advanced liver disease). The most common subgenotype/subtype of HBV was B3/adw (97%). The HBsAg titer was lower in patients with advanced liver disease than that in patients with chronic hepatitis. The MHR variants were grouped based on the percentage of the viral population affected: major, >20% of the total population; intermediate, 5% to <20%; and minor, 1% to <5%. The rates of MHR variation that were present in the major and intermediate viral population were significantly greater in patients with advanced liver disease than those in chronic patients. The most frequent MHR variants related to immune evasion in the major and intermediate populations were P120Q/T, T123A, P127T, Q129H/R, M133L/T, and G145R. The major population of MHR variants causing impaired of HBsAg secretion (e.g., G119R, Q129R, T140I, and G145R) was detected only in advanced liver disease patients. This is the first study to use ultradeep sequencing for the detection of MHR variants of HBV quasispecies in Indonesian patients. We found that a greater number of MHR variations was related to disease severity and reduced likelihood of HBsAg titer.T he high mutation rate of hepatitis B virus (HBV), which is attributable to the lack of a proofreading function in its polymerase and the high replication rate of the virus, induces viral diversity, referred to as viral quasispecies. Many studies have demonstrated that the identification of HBV quasispecies may help predict disease progression and therapeutic outcomes (1-3). Accordingly, HBV variants in the quasispecies pool are probably clinically relevant (4).The surface (S) region used to classify HBV strains is responsible for the expression of hepatitis B surface antigen (HBsAg). HBsAg is the major target for viral neutralization by the immune responses of the host, either naturally or by vaccine-induced antibodies. However, the major hydrophilic region (MHR) located in the central HBsAg, comprising amino acids 100 to 169, contains many discontinuous B-cell epitopes that are recognized by hepatitis B surface antibodies (anti-HBs) (5-7). The exact border of the neutralizing domain of the MHR region is still unclear, although the ␣-determinant region (amino acids 124 to 147) within the MHR has been known to be strongly involved in antibody binding (8,9). Moreover, many studies have noted that variations within the MHR can alter the antigenicity of HBsAg and are responsible for (i) the evasion of vaccine-induced antibodies, (ii) the failure of immu...

show abstract

“…Indeed, field studies of children carrying the Gly-145-Arg mutant have documented its failure to spread to vaccinated family members. 85 Recent models of HBV vaccination have predicted the disappearance of wild-type HBV in 200 years and the emergence of the Gly-145-Arg mutant as a public health threat in 60 years, based on an estimated total lack of cross-protection against the mutant by existing vaccines. 86 Fortunately, the present study demonstrates that this will not be the case.…”

Section: Discussionmentioning

confidence: 99%

Licensed recombinant hepatitis B vaccines protect chimpanzees against infection with the prototype surface gene mutant of hepatitis B virus

et al. 1999

View full text Add to dashboard Cite

The emergence in vaccinated individuals of hepatitis B virus (HBV) mutants with amino acid substitutions within the a determinant of the surface protein has raised the possibility that such variants represent neutralization escape mutants. We previously demonstrated that one such mutant HBV, strain AS, with an arginine substituted for glycine at surface gene codon 145, was infectious and pathogenic in seronegative chimpanzees. In the present study, the protective efficacy of licensed hepatitis B vaccines was evaluated against challenge with this mutant virus.

show abstract

Current aspects of hepatitis B surface antigen mutants in Singapore

Cited by 52 publications

References 25 publications

Change in Hepatitis B Virus Large Surface Antigen Variant Prevalence 13 Years after Implementation of a Universal Vaccination Program in China

Change in Hepatitis B Virus Large Surface Antigen Variant Prevalence 13 Years after Implementation of a Universal Vaccination Program in China

Ultradeep Sequencing for Detection of Quasispecies Variants in the Major Hydrophilic Region of Hepatitis B Virus in Indonesian Patients

Licensed recombinant hepatitis B vaccines protect chimpanzees against infection with the prototype surface gene mutant of hepatitis B virus

Contact Info

Product

Resources

About