phaidra.vetmeduni.ac.at o:4067 DOI 10.1186/s12974-025-03422-6 Neuron-restricted cytomegalovirus latency in the central nervous system regulated by CD4+ T-cells and IFN-γ All human herpesviruses establish latency following the resolution of the primary infection. Among these, α-herpesviruses HSV-1, HSV-2 and VZV establish latency in neurons, whereas neurons are not traditionally considered a site of latency for other herpesviruses. Using a combination of in vivo murine models and ex vivo human fetal tissues, we discovered that cytomegalovirus (CMV), a ubiquitous β-herpesvirus, can persist in neurons and that CD4+ T-cell-derived interferon-gamma is critical in restricting active viral replication in this cell type. Furthermore, we show that mouse CMV can establish latency in neurons and that CD4+ T-cells are essential in preventing viral reactivation. Our findings may have translational significance because human cytomegalovirus (HCMV) is the leading cause of congenital viral infections resulting in neurodevelopmental and neuroinflammatory lesions with long-term functional sequelae. eng Animals Mice Virus Latency Physiology Cytomegalovirus Physiology Cytomegalovirus Immunology CD4-Positive T-Lymphocytes Virology CD4-Positive T-Lymphocytes Immunology Interferon-gamma Metabolism Humans Neurons Virology Neurons Metabolism Mice, Inbred C57BL Central Nervous System Virology Central Nervous System Immunology Cytomegalovirus Infections Immunology 2025-04-17T08:35:50.489Z LOMv1.0 Author BEGIN:VCARD VERSION:3.0 N:Krstanović;Fran; FN:Fran Krstanović END:VCARD BEGIN:VCARD VERSION:3.0 N:Mihalić;Andrea; FN:Andrea Mihalić END:VCARD BEGIN:VCARD VERSION:3.0 N:Rashidi;Ahmad Seyar; FN:Ahmad Seyar Rashidi END:VCARD BEGIN:VCARD VERSION:3.0 N:Sitnik;Katarzyna M.; FN:Katarzyna M. Sitnik X-ORCID:https://orcid.org/0000-0002-6965-0322 END:VCARD BEGIN:VCARD VERSION:3.0 N:Ruzsics;Zsolt; FN:Zsolt Ruzsics END:VCARD BEGIN:VCARD VERSION:3.0 N:Čičin-Šain;Luka; FN:Luka Čičin-Šain END:VCARD BEGIN:VCARD VERSION:3.0 N:Verjans;Georges M. G. M.; FN:Georges M. G. M. Verjans END:VCARD BEGIN:VCARD VERSION:3.0 N:Jonjić;Stipan; FN:Stipan Jonjić END:VCARD BEGIN:VCARD VERSION:3.0 N:Brizić;Ilija; FN:Ilija Brizić END:VCARD https://w3id.org/kim/hcrt/scheme https://w3id.org/kim/hcrt/text Textdokument Text LOMv1.0 yes https://creativecommons.org/licenses/by-nc-nd/4.0 application/pdf 3942823 https://phaidra.vetmeduni.ac.at/o:4067 https://phaidra.vetmeduni.ac.at/api/object/o:4067/thumbnail LOMv1.0 discipline