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Review
. 2022 May 24;10(6):1224.
doi: 10.3390/biomedicines10061224.

Antigen Load and T Cell Function: A Challenging Interaction in HBV Infection

Ilaria Montali  1   2 , Andrea Vecchi  1 , Marzia Rossi  1   2 , Camilla Tiezzi  1   2 , Amalia Penna  1   2 , Valentina Reverberi  1 , Diletta Laccabue  1   2 , Gabriele Missale  1   2 , Carolina Boni  1   2 , Paola Fisicaro  1   2
Affiliations
Review

Antigen Load and T Cell Function: A Challenging Interaction in HBV Infection

Ilaria Montali et al. Biomedicines. .

Abstract

Current treatment for chronic HBV infection is mainly based on nucleos(t)ide analogues, that in most cases need to be administered for a patient's lifetime. There is therefore a pressing need to develop new therapeutic strategies to shorten antiviral treatments. A severe dysfunction of virus-specific T cell responses contributes to virus persistence; hence, immune-modulation to reconstitute an efficient host antiviral response is considered a potential approach for HBV cure. In this perspective, a detailed understanding of the different causes of T cell exhaustion is essential for the design of successful functional T cell correction strategies. Among many different mechanisms which are widely believed to play a role in T cell dysfunction, persistent T cell exposure to high antigen burden, in particular HBsAg, is expected to influence T cell differentiation and function. Definitive evidence of the possibility to improve anti-viral T cell functions by antigen decline is, however, still lacking. This review aims at recapitulating what we have learned so far on the complex T cell-viral antigen interplay in chronic HBV infection.

Keywords: HBsAg; T cells; antigen load; chronic HBV infection.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Schematic representation of HBsAg and HBcrAg production from the HBV-infected hepatocyte. Created with: BioRender.com (accessed on 20 May 2022).
See this image and copyright information in PMC

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References

    1. McLane L.M., Abdel-Hakeem M.S., Wherry E.J. CD8 T cell exhaustion during chronic viral infection and cancer. Annu. Rev. Immunol. 2019;37:457–495. doi: 10.1146/annurev-immunol-041015-055318. - DOI - PubMed
    1. Fisicaro P., Barili V., Rossi M., Montali I., Vecchi A., Acerbi G., Laccabue D., Zecca A., Penna A., Missale G., et al. Pathogenetic mechanisms of T cell dysfunction in chronic HBV infection and related therapeutic approaches. Front. Immunol. 2020;11:849. doi: 10.3389/fimmu.2020.00849. - DOI - PMC - PubMed
    1. Rydell G.E., Prakash K., Norder H., Lindh M. Hepatitis B surface antigen on subviral particles reduces the neutralizing effect of anti-HBs antibodies on hepatitis B viral particles in vitro. Virology. 2017;509:67–70. doi: 10.1016/j.virol.2017.05.017. - DOI - PubMed
    1. Iannacone M., Guidotti L.G. Immunobiology and pathogenesis of hepatitis B virus infection. Nat. Rev. Immunol. 2022;22:19–32. doi: 10.1038/s41577-021-00549-4. - DOI - PubMed
    1. Fanning G.C., Zoulim F., Hou J., Bertoletti A. Author correction: Therapeutic STRATEGIES for hepatitis B virus infection: Towards a cure. Nat. Rev. Drug Discov. 2020;19:291. doi: 10.1038/s41573-019-0057-9. - DOI - PubMed

Grants and funding

This work was supported by a grant from Emilia-Romagna Region, Italy (Programma di Ricerca Regione-Università 2010–2012; PRUa1RI-2012-006), by a grant from the Italian Ministry of Health (Ricerca Finalizzata RF 2013-02359333) and by a PRIN (Progetti di Ricerca di Rilevante Interesse Nazionale) grant (2017MPCWPY_002), Ministry of University and Research.

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