HBV S antigen evolution in the backdrop of HDV infection affects epitope processing and presentation

Mehwish Sajjad, Syed Ali, Samina Baig, Shaheen Sharafat, Bilal Ahmed Khan, Saeed Khan, Muhammad Nouman Mughal, Syed Hani Abidi

Research output: Contribution to journalArticlepeer-review

Abstract

Introduction: HBV can evolve under selection pressure exerted by drugs and/or host immunity, resulting in accumulation of escape mutations that can affect the drug or the immune activity. Hepatitis delta virus (HDV) coinfection is also known to exert selection pressure on HBV, which leads to selective amplification of certain mutations, especially in genes that are required for HDV pathogenesis, such as HBsAg. However, little is known about the function of these mutations on HBV or HDV life cycle. The purpose of this study is to determine mutations selectively amplified in the backdrop of HDV, and how these mutations affect processing of CD4- and CD8-T cell epitopes. Methods: HBsAg was successfully amplified from 49/50 HBV mono- and 36/50 coinfected samples. The sequences were used to identify mutations specific to each study group, followed by an in silico analysis to determine the effect of these mutations on (1) proteasomal degradation, (2) MHC-I and MHC-II biding, and (3) processing of T-cell epitopes. Results: HBV-HDV coinfected sequences exhibited certain unique mutations in HBsAg genes. Some of these mutations affected the generation of proteasomal sites, binding of HBsAg epitopes to MHC-I and -II ligands, and subsequent generation of T- cell epitopes. Conclusion: These observations suggest that HBV selectively amplifies certain mutations in the backdrop of HDV coinfection. Selective amplification of these mutations at certain strategic locations might not only enable HBV to counteract the inhibitory effects of HDV on HBV replication but also facilitate its survival by escaping the immune response.

Original languageEnglish
Pages (from-to)3714-3729
Number of pages16
JournalJournal of Medical Virology
Volume93
Issue number6
DOIs
Publication statusPublished - Jun 2021

Keywords

  • Epitope processing
  • HBV mono-infection
  • HBV-HDV coinfection
  • HBsAg

ASJC Scopus subject areas

  • Virology
  • Infectious Diseases

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