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@ARTICLE{Maassen:302813,
      author       = {F. Maassen and V. T. K. Le-Trilling and L. Betke and T.
                      Bracht and C. Siegmund and M. Bayer and B. Katschinski and
                      A. Belter and T. Becker and D. Mennerich and S. Voigt and L.
                      Frappier and B. Sitek and K. Fleischhauer$^*$ and M.
                      Trilling},
      title        = {{T}he human cytomegalovirus-encoded p{US}28 antagonizes
                      {CD}4+ {T} cell recognition by targeting {CIITA}.},
      journal      = {eLife},
      volume       = {14},
      issn         = {2050-084X},
      address      = {Cambridge},
      publisher    = {eLife Sciences Publications},
      reportid     = {DKFZ-2025-01353},
      pages        = {e96414},
      year         = {2025},
      abstract     = {Human cytomegalovirus (HCMV) is a relevant pathogen,
                      especially for individuals with impaired immunity.
                      Harnessing potent immune antagonists, HCMV circumvents
                      sterile immunity. Given that HCMV prevents the upregulation
                      of human leukocyte antigen (HLA)-DP and HLA-DR, we screened
                      a library of HCMV genes by co-expression with the HLA class
                      II (HLA-II)-inducing transcription coordinator class II
                      transactivator (CIITA). We identified the latency regulator
                      pUS28 as an interaction factor and potent viral antagonist
                      of CIITA-driven expression of CD74, HLA-DR, HLA-DM, HLA-DQ,
                      and HLA-DP. Both wt-pUS28 and a mutant incapable of inducing
                      G protein-coupled signaling (R129A), but not a mutant
                      lacking the C-terminus, drastically reduced the CIITA
                      protein abundance post-transcriptionally. While control CD4
                      + T cells from HCMV-seropositive individuals vigorously
                      responded to CIITA-expressing cells decorated with HCMV
                      antigens, pUS28 expression was sufficient to inhibit HLA-II
                      induction and immune recognition by HCMV-specific CD4 + T
                      cells. Our data uncover pUS28 to be employed by HCMV to
                      evade HLA-II-mediated recognition by CD4 + T cells.},
      keywords     = {Humans / Trans-Activators: metabolism / Trans-Activators:
                      antagonists $\&$ inhibitors / Trans-Activators: genetics /
                      Cytomegalovirus: genetics / Cytomegalovirus: immunology /
                      CD4-Positive T-Lymphocytes: immunology / Nuclear Proteins:
                      metabolism / Nuclear Proteins: antagonists $\&$ inhibitors /
                      Nuclear Proteins: genetics / Viral Proteins: metabolism /
                      Viral Proteins: genetics / Host-Pathogen Interactions / CD4+
                      T cells (Other) / CD74 (Other) / CIITA (Other) / G
                      protein-coupled receptor (Other) / GPCR (Other) / HCMV
                      (Other) / HHV-5 (Other) / HLA class II (Other) / HLA-DP
                      (Other) / HLA-DR (Other) / Human cytomegalovirus (Other) /
                      M33 (Other) / US28 (Other) / human herpesvirus 5 (Other) /
                      infectious disease (Other) / latency (Other) / microbiology
                      (Other) / viruses (Other) / Trans-Activators (NLM Chemicals)
                      / MHC class II transactivator protein (NLM Chemicals) /
                      Nuclear Proteins (NLM Chemicals) / Viral Proteins (NLM
                      Chemicals)},
      cin          = {ED01},
      ddc          = {600},
      cid          = {I:(DE-He78)ED01-20160331},
      pnm          = {899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:40608405},
      pmc          = {pmc:PMC12226020},
      doi          = {10.7554/eLife.96414},
      url          = {https://inrepo02.dkfz.de/record/302813},
}