https://phaidra.vetmeduni.ac.at/o:4067 Neuron-restricted cytomegalovirus latency in the central nervous system regulated by CD4+ T-cells and IFN-γ Krstanović, Fran Fran Krstanović Mihalić, Andrea Andrea Mihalić Rashidi, Ahmad Seyar Ahmad Seyar Rashidi Sitnik, Katarzyna M. Katarzyna M. Sitnik 0000-0002-6965-0322 University of Veterinary Medicine Vienna Ruzsics, Zsolt Zsolt Ruzsics Čičin-Šain, Luka Luka Čičin-Šain Verjans, Georges M. G. M. Georges M. G. M. Verjans Jonjić, Stipan Stipan Jonjić Brizić, Ilija Ilija Brizić BMC journal article open access eng 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. 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 http://creativecommons.org/licenses/by-nc-nd/4.0/ https://phaidra.vetmeduni.ac.at/api/object/o:4067/download 10.1186/s12974-025-03422-6 https://phaidra.vetmeduni.ac.at/o:605 application/pdf Journal of Neuroinflammation issn:1742-2094 VoR Journal of Neuroinflammation 22 1 3.76 MB 2025