Mutations in the S-gene affecting the immunologic determinants of the envelope protein of hepatitis B virus

Lee, Hyo‐Suk; Ulrich, Paul P.; Vyas, Girish N.

doi:10.1016/0168-8278(91)90035-a

Cited by 9 publications

(5 citation statements)

References 22 publications

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“…The in vivo mutation rate of hepadna virus was estimated to be lower than that of RNA viruses and higher than that of DNA viruses 28) . Presumably, such a high frequency of mutation is a result of HBV replication via reverse transcription of a RNA intermediate 29) .…”

Section: Discussionmentioning

confidence: 93%

Association of the Core Clustering Mutations Codon 21-34 and the Severity of Chronic Hepatitis B in Korean Patients

Koh

Lee²,

Kim³

1995

Korean J Intern Med

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Objectives:There are regions in the core gene of hepatitis B virus (HBV) where missense mutations are clustered, and mutations in that region are related to severe liver disease. However, there were some differences of the major regions for mutation clustering among ethnic groups. To explore the phenomenon of clustering mutations in Korean patients with chronic HBV infection and to elucidate the correlation between clustering mutation region of the core gene and the severity of liver damage, we analyzed the precore/core gene sequence of HBV in the sera from fifteen chronic hepatitis B (CH-B) patients.Methods:We analysed the HBV precore and core sequences in the sera obtained from fifteen patients (14 males and 1 female, mean age 30.0 years) with biopsy-proven CH-B. The patients were divided into two groups according to the pathological severity of CH-B; namely, group I consisted of 8 patients with chronic persistent hepatitis (CPH), and group II included 7 patients with chronic active hepatitis (CAH). After extraction of HBV DNA from each serum by proteinase K and phenol-chloroform solution, the entire precore and core region of HBV was amplified by PCR, and then the PCR products were subjected to direct sequencing using thermostable DNA polymerase. Fisher’s exact test and Mann-Whitney U test were used for statistical analysis.Results:A total of 181 nucleotide substitutions were found in the HBV core gene from the 15 CH-B patients, of which 23 were missense and 158 were silent. The nucleotide and amino acid substitution rates were not significantly different between the two groups (p>0.05). Two mutational hot spots (MHS), codons 21–34 (MHS1) and codons 85–100 (MHS2), were found in the deduced amino acid alignment of the core gene. The alteration rate of amino acid residue in these regions were 2.857×10−2 and 5.000×10−2, respectively. Of 8 CPH patients, 5 showed missense mutations only in MHS2. In comparison, of 7 CAH patients, 3 showed them both in MHS1 and MHS2, 1 only in MHS1, and 1 only in MHS2; thus, missense mutation in MHS1 was exclusively found in patient with CAH.Conclusions:There were two mutation clusterings in the core region of adr subtype of HBV from Korean CH-B patients. Mutations in MHS1 (codon 21–34), but not in MHS2 (codon 85–100), are more likely to be related to the severity of CH-B. A longitudinal study using sequential samples is warranted to further clarify the role of MHS1 in the pathogenesis of more severe CH-B.

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Section: Discussionmentioning

confidence: 93%

Association of the Core Clustering Mutations Codon 21-34 and the Severity of Chronic Hepatitis B in Korean Patients

Koh

Lee²,

Kim³

1995

Korean J Intern Med

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“…As such, HBsAg may be not measurable, and infection may occur even after HBV vaccination [27]. Among these mutations, the codon 145 mutation is known to be the most frequent [27,28]. The pre-S gene region of the HBV is known to serve a major role in the multiplication and etiology of the virus.…”

Section: Discussionmentioning

confidence: 99%

Study on hepatitis B virus pre-S/S gene mutations of renal tissues in children with hepatitis B virus-associated membranous nephropathy

2006

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This study aims to clarify the prevalence and significance of the emergence of hepatitis B virus (HBV) pre-S/S mutations in children with hepatitis B virus-associated membranous nephropathy (HBVMN). Direct sequencing of polymerase chain reaction products of renal tissue samples that were obtained via percutaneous renal biopsy from seven children revealed the presence of HBV DNA. Seven adr subtypes were analyzed. Deletions in the HBV pre-S region were observed once per seven patients. The deletions were noted in both the pre-S1 (27 bp) and pre-S2 (60 bp) regions. Various point mutations in the HBV pre-S region were detected in all seven patients and proved to be more frequent in the pre-S1 region than in the S2 region. Point mutations in the HBV S region were detected in six patients. Among these mutations, the mutation in the "a" determinant region was noted in five patients. No deletion, however, was observed in the HBV S region. These observations suggested that deletions and point mutations in the HBV pre-S1 and pre-S2 regions and point mutations in the HBV S region, especially the "a" determinant region, are common frequent findings. These results also suggested that HBV pre-S/S region mutations may be involved in the pathogenesis in children with HBVMN.

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“…Although the subtypes are useful as epidemiological tracers of infection, they are of no pathogenetic significance. The resolution of any HBV infection culminates in production of anti-HBs, a long-lasting antibody response against the ''a'' determinant(s) of HBsAg, which confers lifelong immunity against all serotypes of HBV (5,44,45). In contrast, a failure of the immune response to the HBsAg ''a'' determinant establishes a persistent infection and leads to a spectrum of conditions with or without disease (82).…”

Section: Hepatitis Bmentioning

confidence: 99%

“…Because the overlapping S and P genes are transcribed in different open reading frames, we proposed in 1982 the concept of replication-competent HBV DNA arising from point mutations in the DNA sequence encoding the nine amino acid residues 139 to 147, which determine the immunoreactivity of the ''a'' determinant of HBsAg (5,82,84). Such genetic variants with amino acid substitutions in these nine residues of HBsAg could bestow a conformational change adequate to allow escape from the otherwise neutralizing anti-HBs (44). Although recombinant HBsAg used in a monoclonal vaccine against HBV induces a potent anti-HBs response and provides protection against infection with HBV of all sero-types, Carman et al (14) have reported a vaccine-induced escape mutant of HBV in successfully vaccinated children who had simultaneously circulating HBsAg and anti-HBs.…”

Section: Hepatitis Bmentioning

confidence: 99%

“…Sequence analysis demonstrated that an escape mutant from one of the children had undergone a glycine-to-arginine substitution at position 145 (14,32,86). This substitution may have caused a conformational change in an external loop of HBsAg so that the vaccine-induced anti-HBs could not bind to the mutant HBsAg, thus allowing HBV to replicate in the presence of a normal antibody response against the HBV envelope protein (44). Similar mutants have been found in Japan and The Gambia, suggesting that the immune escape mutant of HBV can occur worldwide (29,88).…”

Section: Hepatitis Bmentioning

confidence: 99%

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Immunodiagnosis of viral hepatitides A to E and non-A to -E

Yang

Vyas

1996

Clin Diagn Lab Immunol

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Primary viral infection of liver cells is caused by several distinct hepatotropic viruses transmitted by oral and parenteral routes. While the clinical, epidemiological, pathological, and immunological aspects of viral hepatitides have many common attributes and subtle differences (39), the etiologies of liver disorders cannot be established on the basis of clinical signs and symptoms or abnormal liver function tests (e.g., elevated alanine aminotransferase [ALT]). Following the discovery of Australia antigen (8), which was subsequently termed hepatitis B surface antigen (HBsAg), the identification and characterization of hepatitis B virus (HBV), hepatitis A virus (HAV),

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Mutations in the S-gene affecting the immunologic determinants of the envelope protein of hepatitis B virus

Cited by 9 publications

References 22 publications

Association of the Core Clustering Mutations Codon 21-34 and the Severity of Chronic Hepatitis B in Korean Patients

Association of the Core Clustering Mutations Codon 21-34 and the Severity of Chronic Hepatitis B in Korean Patients

Study on hepatitis B virus pre-S/S gene mutations of renal tissues in children with hepatitis B virus-associated membranous nephropathy

Immunodiagnosis of viral hepatitides A to E and non-A to -E

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