Fran Krstanović Fran Krstanović Andrea Mihalić Andrea Mihalić Ahmad Seyar Rashidi Ahmad Seyar Rashidi Katarzyna M. Sitnik Katarzyna M. Sitnik Zsolt Ruzsics Zsolt Ruzsics Luka Čičin-Šain Luka Čičin-Šain Georges M. G. M. Verjans Georges M. G. M. Verjans Stipan Jonjić Stipan Jonjić Ilija Brizić Ilija Brizić BMC 2025 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. PDFDocument eng 2025-04-17T08:35:49.944997Z 2025 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 3942823 b application/pdf http://creativecommons.org/licenses/by-nc-nd/4.0/