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Dehn, S.* ; Burkhard, R.* ; Leyens, J.* ; Kaiser, T.* ; Brandimarte, S.* ; Heiligensetzer, D.* ; Koppensteiner, H. ; Bajoghli, B.* ; Hailfinger, S.* ; Schilbach, K.* ; Schindler, M.

HIV-1 manipulates CD96 on CD4+ T cells to subvert antiviral immunity.

Sci. Adv. 11:eadx7485 (2025)
Verlagsversion Forschungsdaten DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
HIV-1 evades immune responses by modulating plasma membrane receptors. Using a flow cytometry-based screening, we profiled 332 surface receptors on HIV-1-infected primary CD4+ T cells and identified 23 down-regulated receptors, including known targets such as CD4, MHCI, CCR7, and CD62L. CD96, an inhibitory natural killer (NK) cell receptor poorly studied in human CD4+ T cells, was markedly down-regulated. This modulation, mediated by the viral proteins Nef and Vpu, surpassed that of other NK-associated receptors such as CD155 and NTB-A and is conserved across lentiviruses. CD96Hi CD4+ T cells exhibited a proinflammatory TH1/TH17 phenotype characterized by IFN-γ and IL-17 secretion and displayed impaired migration in vivo. Furthermore, CD96 ligation enhanced IFN-γ release upon viral peptide stimulation and promoted the secretion of TH1/TH17-associated cytokines. Our findings suggest that CD96 regulates antiviral immune responses and maintains proinflammatory properties in CD4+ T cells. Thus, its down-regulation represents a previously unknown HIV-1 immune evasion strategy, with implications for exploiting CD96 as immunotherapeutic target.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Human-immunodeficiency-virus; Down-modulation; Type-1 Nef; Surface Expression; Vpu; Receptor; Protein; Activation; Adhesion; Tigit
ISSN (print) / ISBN 2375-2548
e-ISSN 2375-2548
Zeitschrift Science Advances
Quellenangaben Band: 11, Heft: 36, Seiten: , Artikelnummer: eadx7485 Supplement: ,
Verlag American Association for the Advancement of Science (AAAS)
Verlagsort Washington, DC [u.a.]
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Virology (VIRO)
Förderungen Helmholtz Center Munich
University Hospital Tubingen
Deutsche Forschungsgemeinschaft