%0 Journal Article
%A Maassen, Fabienne
%A Le-Trilling, Vu Thuy Khanh
%A Betke, Luisa
%A Bracht, Thilo
%A Siegmund, Corinna
%A Bayer, Malte
%A Katschinski, Benjamin
%A Belter, Antonia
%A Becker, Tanja
%A Mennerich, Denise
%A Voigt, Sebastian
%A Frappier, Lori
%A Sitek, Barbara
%A Fleischhauer, Katharina
%A Trilling, Mirko
%T The human cytomegalovirus-encoded pUS28 antagonizes CD4+ T cell recognition by targeting CIITA.
%J eLife
%V 14
%@ 2050-084X
%C Cambridge
%I eLife Sciences Publications
%M DKFZ-2025-01353
%P e96414
%D 2025
%X 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.
%K Humans
%K Trans-Activators: metabolism
%K Trans-Activators: antagonists & inhibitors
%K Trans-Activators: genetics
%K Cytomegalovirus: genetics
%K Cytomegalovirus: immunology
%K CD4-Positive T-Lymphocytes: immunology
%K Nuclear Proteins: metabolism
%K Nuclear Proteins: antagonists & inhibitors
%K Nuclear Proteins: genetics
%K Viral Proteins: metabolism
%K Viral Proteins: genetics
%K Host-Pathogen Interactions
%K CD4+ T cells (Other)
%K CD74 (Other)
%K CIITA (Other)
%K G protein-coupled receptor (Other)
%K GPCR (Other)
%K HCMV (Other)
%K HHV-5 (Other)
%K HLA class II (Other)
%K HLA-DP (Other)
%K HLA-DR (Other)
%K Human cytomegalovirus (Other)
%K M33 (Other)
%K US28 (Other)
%K human herpesvirus 5 (Other)
%K infectious disease (Other)
%K latency (Other)
%K microbiology (Other)
%K viruses (Other)
%K Trans-Activators (NLM Chemicals)
%K MHC class II transactivator protein (NLM Chemicals)
%K Nuclear Proteins (NLM Chemicals)
%K Viral Proteins (NLM Chemicals)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:40608405
%2 pmc:PMC12226020
%R 10.7554/eLife.96414
%U https://inrepo02.dkfz.de/record/302813