Role of surface promoter mutations in hepatitis B surface antigen production and secretion in occult hepatitis B virus infection

Sengupta, Sonali; Rehman, Shagufta; Durgapal, Hemlata; Acharya, Subrat Kumar; Panda, Subrat Kumar

doi:10.1002/jmv.20790

Cited by 31 publications

(25 citation statements)

References 37 publications

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“…Alternatively, mutants resulted in decreasing the quantity of HBsAg secretion below the sensitivity of standard enzyme-linked immunosorbent assay but just enough for viral assembly may be the other explanation. Previously, Chaudhuri et al found similar pre-S variant from occult HBV carriers and demonstrated that deletion of S promoter would alter the ratio of large and small surface proteins and decrease the circulating HBsAg level [25,30] could normally replicate and be competent in HBsAg production [31]. Accordingly, they proposed that the host, rather than the viral factors, is responsible for occult HBV infection.…”

Section: Discussionmentioning

confidence: 96%

Occult hepatitis B virus infection in hepatitis B vaccinated children in Taiwan

Mu¹,

Lin²,

Jow³

et al. 2009

Journal of Hepatology

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Section: Discussionmentioning

confidence: 96%

Occult hepatitis B virus infection in hepatitis B vaccinated children in Taiwan

Mu¹,

Lin²,

Jow³

et al. 2009

Journal of Hepatology

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“…In transgenic mice, inhibition of HBsAg secretion has been related to the occurrence of cell injury mediated by interferon-␥ [24] . Furthermore, an association has been proposed between HBsAg secretion inhibition and occult HBV infection [25] . Among 1,220 HBV sequences available in databanks, only two (sequence accession numbers AY311358 [genotype F] and AF090842 [genotype A]) exhibited an amino acid variation at residue 215.…”

Section: Figmentioning

confidence: 99%

A Unique Amino Acid Substitution, L215Q, in the Hepatitis B Virus Small Envelope Protein of a Genotype F Isolate That Inhibits Secretion of Hepatitis B Virus Subviral Particles

Araújo

Vianna²,

Soares³

et al. 2008

Intervirology

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The small (S) envelope protein is the major component of hepatitis B virus surface antigen (HBsAg). Some mutations in the S-HBsAg coding region may cause deficiency in the secretion of both viral and empty subviral particles (SVPs) and lead to accumulation of HBsAg inside the cells. In this study, we identified a unique amino acid substitution (L215Q) in the carboxyl-terminal end of S-HBsAg of an HBV genotype F isolate that provoked an inhibitory effect on secretion of SVPs. HBsAg levels were measured daily by enzyme-linked immunosorbent assay in the medium and cell extracts of HuH7 and CHO cells transiently transfected with plasmids containing wild-type or mutated S-HBsAg gene. Wild-type HBsAg was detectable in both medium and cell extracts of transfected cells. In contrast, extracellular levels of mutant HBsAg were not higher than cut-off values. By immunofluorescence with monoclonal antibody, it was shown that wild-type HBsAg was distributed throughout the cytoplasm, whereas mutant HBsAg was concentrated around the nucleus, suggesting retention in the endoplasmic reticulum. Amino acid substitutions that inhibit HBsAg secretion, such as that characterized in this study (L215Q), should have implications in HBV immunological diagnostics.

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“…Besides, several investigations have described mutations clustering in the aforementioned key immunodominant regions of the HBsAg, which are able of decreasing the immune recognition of the virus, structural alteration and various mutations in genomic regulatory regions, leading to a strong reduction of HBsAg expression (4, 5, 7, 22, 24). In a functional survey by Sengupta et al in India, the production, secretion and localization of surface proteins of HBV were studied in HepG2 cells, transfected with the wild-type and mutant pre-S1 and pre-S2/S promoters of HBV molecular clones 313.1.…”

Section: Resultsmentioning

confidence: 99%

Potential Mutations Associated With Occult Hepatitis B Virus Status

2014

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Context:Occult hepatitis B virus (HBV) status (OHBS) is simply defined as the presence of HBV DNA in the liver (with or without detectable HBV DNA in the serum), in the absence of serum HBV surface antigen (HBsAg). Importance of OHBS is mostly clinical, related to its possible role in spreading through blood transfusion and liver transplantation; causing classic forms of HBV. Mechanisms underlying this entity are poorly defined. Several possibilities have been suggested, with major classification into two groups: defective host immune response and viral replication activity through mutations of HBV DNA sequence. Mutations are extensively investigated in all four overlapping open reading frames (ORFs) of HBV genome, to define their possible role in the pathogenesis of OHBS. Some of these mutations like S-escape mutants could not be detected by the routine available assays, making them difficult to diagnosis. Therefore, trying to detect this covert condition could be more helpful for defining better preventive and therapeutic strategies.Evidence Acquisition:In the present study we provided an in-depth review of the most important new data available on different mutations in HBV genome of patients with OHBS, which may play a role in the pathogenesis of OHBS. The data were collected through reviewing the full-text articles, identified by the PubMed search, using the following keywords and their different combinations: occult hepatitis B, HBV genome, "a" determinant, HBV open reading frames, S mutations, X mutations, P mutations and C mutations.Results:Variants within the major hydrophilic region (MHR) of the HBsAg, deletions in the pre-S1region, codon stop in the S open reading frames (ORF), sporadic non common mutations, some mutations affecting the posttranslational production of HBV proteins in the S ORF like deletion mutations, mutations in start codon and nucleotide changes in the X ORF, deletion and point mutations in P ORF and sometimes, nucleotide substitution in the C ORF are among the assumed mutations detected to have a role in OHBS appearance.Conclusions:Studies mostly lacked a control group and the whole-length HBV sequencing was scant with conflicting results, suggesting that OHBS is often a result of multiple mechanisms. Additional studies on full-length HBV genomes from occult and non-occult HBV cases may shed more light on the interplay between different mechanisms involved in the pathogenesis of OHBS.

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Role of surface promoter mutations in hepatitis B surface antigen production and secretion in occult hepatitis B virus infection

Cited by 31 publications

References 37 publications

Occult hepatitis B virus infection in hepatitis B vaccinated children in Taiwan

Occult hepatitis B virus infection in hepatitis B vaccinated children in Taiwan

A Unique Amino Acid Substitution, L215Q, in the Hepatitis B Virus Small Envelope Protein of a Genotype F Isolate That Inhibits Secretion of Hepatitis B Virus Subviral Particles

Potential Mutations Associated With Occult Hepatitis B Virus Status

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