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. 2023 Oct;95(10):e29195.
doi: 10.1002/jmv.29195.

Impact of core protein naturally selected mutants associated with HBeAg-negative status in HBV biosynthesis

María Mercedes Elizalde  1   2 , Cecilia Graciela Giadans  1   2 , Rodolfo Héctor Campos  2   3 , Diego Martín Flichman  1   2
Affiliations

Impact of core protein naturally selected mutants associated with HBeAg-negative status in HBV biosynthesis

María Mercedes Elizalde et al. J Med Virol. 2023 Oct.

Abstract

Hepatitis B e antigen (HBeAg) loss represents a late stage of chronic hepatitis B virus (HBV) infection associated with a drastic decrease in HBV-DNA, a lower risk of disease progression, and the occurrence of several mutations in the preCore/core region. However, the underlying mechanisms supporting the downregulation of viral replication have yet to be elucidated. In the present study, the analysis of the frequency of subgenotype D1 core protein (HBc) mutations associated with HBeAg status revealed a higher mutation rate in HBeAg-negative sequences compared to HBeAg-positive ones. Particularly, 22 amino acids exhibited a higher frequency of mutation in HBeAg-negative sequences, while the remaining residues showed a high degree of conservation. Subsequently, the assessment of HBc mutants derived from HBeAg-negative patients in viral structure and replicative capacity revealed that HBc mutations have the ability to modulate the subcellular localization of the protein (either when the protein was expressed alone or in the context of viral replication), capsid assembly, and, depending on specific mutation patterns, alter covalently closed circular DNA (cccDNA) recycling and up- or downregulate viral replication. In conclusion, HBc mutations associated with HBeAg-negative status impact on various stages of the HBV life cycle modulating viral replication during the HBeAg-negative stage of infection.

Keywords: HBeAg seroconversion; core protein; hepatitis B virus; mutations.

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References

REFERENCES

    1. Sheena BS, Hiebert L, Han H, et al. Global, regional, and national burden of hepatitis B, 1990-2019: a systematic analysis for the global burden of disease study 2019. Lancet Gastroenterol Hepatol. 2022;7(9):796-829. doi:10.1016/S2468-1253(22)00124-8
    1. Zeng DY, Li JM, Lin S, et al. Global burden of acute viral hepatitis and its association with socioeconomic development status, 1990-2019. J Hepatol. 2021;75(3):547-556. doi:10.1016/j.jhep.2021.04.035
    1. Tsukuda S, Watashi K. Hepatitis B virus biology and life cycle. Antiviral Res. 2020;182:104925. doi:10.1016/j.antiviral.2020.104925
    1. Luo Y, Cheng J, Hu Z, et al. Identification of hepatitis B virus core protein residues critical for capsid assembly, pgRNA encapsidation and resistance to capsid assembly modulators. Antiviral Res. 2021;191:105080. doi:10.1016/j.antiviral.2021.105080
    1. Zhao Q, Hu Z, Cheng J, et al. Hepatitis B virus core protein dephosphorylation occurs during pregenomic RNA encapsidation. J Virol. 2018;92(13):e02139-17. doi:10.1128/JVI.02139-17

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