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@ARTICLE{Cirac:178375,
      author       = {A. Cirac and R. Poirey$^*$ and M. Dieckmeyer and K. Witter
                      and H.-J. Delecluse$^*$ and U. Behrends and J. Mautner},
      title        = {{I}mmunoinformatic {A}nalysis {R}eveals {A}ntigenic
                      {H}eterogeneity of {E}pstein-{B}arr {V}irus {I}s
                      {I}mmune-{D}riven.},
      journal      = {Frontiers in immunology},
      volume       = {12},
      issn         = {1664-3224},
      address      = {Lausanne},
      publisher    = {Frontiers Media},
      reportid     = {DKFZ-2022-00025},
      pages        = {796379},
      year         = {2021},
      note         = {#EA:F100#},
      abstract     = {Whole genome sequencing of Epstein-Barr virus (EBV)
                      isolates from around the world has uncovered pervasive
                      strain heterogeneity, but the forces driving strain
                      diversification and the impact on immune recognition
                      remained largely unknown. Using a data mining approach, we
                      analyzed more than 300 T-cell epitopes in 168 published EBV
                      strains. Polymorphisms were detected in approximately $65\%$
                      of all CD8+ and $80\%$ of all CD4+ T-cell epitopes and these
                      numbers further increased when epitope flanking regions were
                      included. Polymorphisms in CD8+ T-cell epitopes often
                      involved MHC anchor residues and resulted in changes of the
                      amino acid subgroup, suggesting that only a limited number
                      of conserved T-cell epitopes may represent generic target
                      antigens against different viral strains. Although
                      considered the prototypic EBV strain, the rather low degree
                      of overlap with most other viral strains implied that B95.8
                      may not represent the ideal reference strain for T-cell
                      epitopes. Instead, a combinatorial library of consensus
                      epitopes may provide better targets for diagnostic and
                      therapeutic purposes when the infecting strain is unknown.
                      Polymorphisms were significantly enriched in epitope versus
                      non-epitope protein sequences, implicating immune selection
                      in driving strain diversification. Remarkably, CD4+ T-cell
                      epitopes in EBNA2, EBNA-LP, and the EBNA3 family appeared to
                      be under negative selection pressure, hinting towards a
                      beneficial role of immune responses against these latency
                      type III antigens in virus biology. These findings validate
                      this immunoinformatics approach for providing novel insight
                      into immune targets and the intricate relationship of host
                      defense and virus evolution that may also pertain to other
                      pathogens.},
      keywords     = {Epstein-Barr virus (Other) / T-cell epitope (Other) /
                      immunoinformatics (Other) / strain variants (Other) / virus
                      evolution (Other)},
      cin          = {F100},
      ddc          = {610},
      cid          = {I:(DE-He78)F100-20160331},
      pnm          = {316 - Infektionen, Entzündung und Krebs (POF4-316)},
      pid          = {G:(DE-HGF)POF4-316},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:34975903},
      pmc          = {pmc:PMC8716887},
      doi          = {10.3389/fimmu.2021.796379},
      url          = {https://inrepo02.dkfz.de/record/178375},
}