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Viral diversity influences T-cell responses to enteric human adenoviruses F40 and F41

Holly M Craven1,2, Jennifer P Hoang1, Rookmini Mukhopadhyay1

  • 1Department of Genetics, Downing Street, University of Cambridge, Cambridge, CB2 3EH, United Kingdom.

Virus Evolution
|January 23, 2026
PubMed

Insights

Human enteric adenoviruses (HAdV-F) evolve to evade immune responses. This study identifies conserved T-cell epitopes in HAdV-F capsid proteins, crucial for understanding viral evolution and designing new vaccines.

Area of Science:

  • Immunology
  • Virology
  • Genomics

Background:

  • Human enteric species F adenoviruses (HAdV-F) cause significant pediatric illness globally.
  • Cellular immune responses, including cytotoxic T cells and cytokines, are vital for controlling HAdV-F infections.
  • HAdV-F capsid proteins (hexon, penton) may evolve to evade host immune detection.

Purpose of the Study:

  • To investigate the evolution of HAdV-F capsid proteins (hexon and penton) in response to cellular immunity.
  • To predict and analyze Major Histocompatibility Complex (MHC) binding epitopes within HAdV-F proteins.
  • To assess the immunogenicity of predicted T-cell epitopes from emergent HAdV-F strains.

Main Methods:

  • Global HAdV genomic data analysis to predict MHC Class I peptide binding in hexon and penton proteins.
  • Focus on MHC Class I alleles prevalent in the UK and Kenya to identify epitopes.
  • Synthesis and testing of F41 hexon peptides for interferon gamma (IFN-γ) responses in healthy donor peripheral blood mononuclear cells (PBMCs).

Main Results:

  • Identification of shared and genotype-specific MHC Class I epitopes across HAdV species C and F.
  • Confirmation of ubiquitous IFN-γ and Interleukin-2 (IL-2) responses to HAdV-F in healthy adults.
  • Significant IFN-γ responses observed in PBMCs against 11 out of 16 predicted F41 hexon epitopes.

Conclusions:

  • HAdV-F-40 and F41 hexon and penton proteins possess conserved, genotype-specific Class I epitopes with potential for vaccine development.
  • Emergent HAdV-F strains contain T-cell epitopes capable of eliciting inflammatory cytokine responses.
  • Further research into T-cell recognition's role in enteric adenovirus evolution is warranted.
Abstract

Keywords:
T celladenovirusepitopesevolution

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