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Mutations in the S gene of hepatitis B virus in three generations of patients with chronic hepatitis B

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Abstract

Failure to neutralize HBsAg and subsequent escape from the host immune system may be caused by HBsAg mutations, particularly in the "a" determinant, which alters the antigenicity of the protein. The purpose of this study was to examine the frequency of S gene mutations in three generations of HBV cases in northeastern Iran. In this study, 90 patients with chronic HBV were assigned to three groups according to the inclusion criteria. The plasma were utilized to extract viral DNA, and the PCR was applied. Direct sequencing and alignment were performed on the S gene, using reference sequence. The results indicated that all HBV genomes were categorized as the genotype D/ayw2. Among 79 point mutations detected, 36.8% were silent, and 56.2% were missense. In the S region, mutations were observed in 88.9% of CHB subjects studied. In the three-generation group, 21.5% of mutations were in the "a" determinant, and 2.6%, 19.5%, and 87.0% of these mutations were observed in antigenic epitopes of CTLs, CD4+, and B cells, respectively. In addition, 56.7% of mutations occurred at Major Hydrophilic Region. S143L and G145R mutations which the most prevalent in the three-generation (36.7%, 20%), and two-generation (42.5%, 20%) groups, related to the failure of HBsAg detection, vaccine, and immunotherapy escape. The findings showed that most of the mutations were concentrated in the B cell epitope. Most CHB cases from the three-generation, especially grandmothers, had HBV S gene mutations and subsequent amino acid mutations, suggesting that these mutations may be critical for pathogenesis and vaccine evasion.

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Abbreviations

HBV:

Hepatitis B virus

HBsAg:

Hepatitis B surface antigen

ORFs:

Open reading frames

ALT:

Alanine transaminase

AST:

Aspartate transaminase

ALP:

Alkaline phosphatase

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Acknowledgements

These results are extracted from the doctoral dissertation of Malihe Naderi. The authors would like to thank everyone who helped them with this research.

Funding

This research did not receive a specific grant from any public, private, or non-profit funding agency.

Author information

Authors and Affiliations

  1. Department of Microbiology and Microbial Biotechnology, Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, Tehran, Iran

    Malihe Naderi & Seyed Masoud Hosseini

  2. Infectious Diseases Research Center, Golestan University of Medical Sciences, Gorgān, Iran

    Malihe Naderi

  3. Biostatistics and Epidemiology Department, Faculty of Health, Health Management and Social Development Research Center, Golestan University of Medical Sciences, Golestan, Iran

    Naser Behnampour

  4. Department of Pediatrics, Faculty of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran

    Iraj Shahramian

  5. Department of Microbiology, Faculty of Medicine, Golestan University of Medical Sciences, Gorgān, Iran

    Abdolvahab Moradi

Authors
  1. Malihe Naderi
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  3. Naser Behnampour
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  4. Iraj Shahramian
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  5. Abdolvahab Moradi
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Contributions

Writing the manuscript: A.M., SMH, MN; carrying out the experiments: MN; conceiving and planning the experiments: A.M., SMH, I.SH, SB; data analysis: A.M., NB, MN; reading and approving the final version of the manuscript: A.M., SMH, MN; revision: A.M., MN.

Corresponding authors

Correspondence to Seyed Masoud Hosseini or Abdolvahab Moradi.

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Competing interest

There are no conflicts of interest declared by the authors. All authors have perused and verified the manuscript's content.

Ethical approval

The Ethics Committee of Golestan University of Medical Sciences approved the current study with the Ethics code of IR. GOUMS.REC.1399.105.

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Edited by Juergen Richt.

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Naderi, M., Hosseini, S.M., Behnampour, N. et al. Mutations in the S gene of hepatitis B virus in three generations of patients with chronic hepatitis B. Virus Genes 59, 662–669 (2023). https://doi.org/10.1007/s11262-023-02012-z

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  • DOI: https://doi.org/10.1007/s11262-023-02012-z

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