Angulo, GuillemZeleznjak, JelenaMartínez Vicente, PabloPuñet Ortiz, JoanHengel, HartmutMesserle, MartinOxenius, AnnetteJonjic, StipanKrmpotić, AstridEngel Rocamora, PabloAngulo Aguado, Ana2023-03-162023-03-162021-01-182050-084Xhttps://hdl.handle.net/2445/195421Viral infections are controlled, and very often cleared, by activated T lymphocytes. The inducible co-stimulator (ICOS) mediates its functions by binding to its ligand ICOSL, enhancing T-cell activation and optimal germinal center (GC) formation. Here, we show that ICOSL is heavily downmodulated during infection of antigen-presenting cells by different herpesviruses. We found that, in murine cytomegalovirus (MCMV), the immunoevasin m138/fcr-1 physically interacts with ICOSL, impeding its maturation and promoting its lysosomal degradation. This viral protein counteracts T-cell responses, in an ICOS-dependent manner, and limits virus control during the acute MCMV infection. Additionally, we report that blockade of ICOSL in MCMV-infected mice critically regulates the production of MCMV-specific antibodies due to a reduction of T follicular helper and GC B cells. Altogether, these findings reveal a novel mechanism evolved by MCMV to counteract adaptive immune surveillance, and demonstrates a role of the ICOS:ICOSL axis in the host defense against herpesviruses.38 p.application/pdfengcc-by (c) Angulo, Guillem et al., 2021https://creativecommons.org/licenses/by/4.0/AntígensCitomegalovirusHerpesvirusImmunitat cel·lularInflamacióCèl·lules TMalalties víriquesRatolins (Animals de laboratori)AntigensCytomegalovirusesHerpesvirusesCellular immunityInflammationT cellsVirus diseasesMice (Laboratory animals)info:eu-repo/semantics/article7105802023-03-16info:eu-repo/semantics/openAccess33459589