Neuron-restricted cytomegalovirus latency in the central nervous system regulated by CD4+ T-cells and IFN-γ
Abstract 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...
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| Format: | Article |
| Language: | English |
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BMC
2025-03-01
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| Series: | Journal of Neuroinflammation |
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| Online Access: | https://doi.org/10.1186/s12974-025-03422-6 |
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| author | Fran Krstanović Andrea Mihalić Ahmad Seyar Rashidi Katarzyna M. Sitnik Zsolt Ruzsics Luka Čičin-Šain Georges M. G. M. Verjans Stipan Jonjić Ilija Brizić |
| author_facet | Fran Krstanović Andrea Mihalić Ahmad Seyar Rashidi Katarzyna M. Sitnik Zsolt Ruzsics Luka Čičin-Šain Georges M. G. M. Verjans Stipan Jonjić Ilija Brizić |
| author_sort | Fran Krstanović |
| collection | DOAJ |
| description | Abstract 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. |
| format | Article |
| id | doaj-art-847f8e5b41fe4248b3d2ed1c7d612963 |
| institution | DOAJ |
| issn | 1742-2094 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Neuroinflammation |
| spelling | doaj-art-847f8e5b41fe4248b3d2ed1c7d6129632025-08-20T02:49:25ZengBMCJournal of Neuroinflammation1742-20942025-03-0122111610.1186/s12974-025-03422-6Neuron-restricted cytomegalovirus latency in the central nervous system regulated by CD4+ T-cells and IFN-γFran Krstanović0Andrea Mihalić1Ahmad Seyar Rashidi2Katarzyna M. Sitnik3Zsolt Ruzsics4Luka Čičin-Šain5Georges M. G. M. Verjans6Stipan Jonjić7Ilija Brizić8Center for Proteomics, Faculty of Medicine, University of RijekaCenter for Proteomics, Faculty of Medicine, University of RijekaHerpeslabNL of the Department of Viroscience, Erasmus Medical CenterDepartment of Biological Sciences and Pathobiology, University of Veterinary Medicine ViennaInstitute of Virology, Faculty of Medicine, University Medical Center Freiburg, University of FreiburgDepartment of Viral Immunology, Helmholtz Centre for Infection ResearchHerpeslabNL of the Department of Viroscience, Erasmus Medical CenterCenter for Proteomics, Faculty of Medicine, University of RijekaCenter for Proteomics, Faculty of Medicine, University of RijekaAbstract 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.https://doi.org/10.1186/s12974-025-03422-6CytomegalovirusCongenital CMVViral latencyNeuronsCD4+ T-cellsHippocampus |
| spellingShingle | Fran Krstanović Andrea Mihalić Ahmad Seyar Rashidi Katarzyna M. Sitnik Zsolt Ruzsics Luka Čičin-Šain Georges M. G. M. Verjans Stipan Jonjić Ilija Brizić Neuron-restricted cytomegalovirus latency in the central nervous system regulated by CD4+ T-cells and IFN-γ Journal of Neuroinflammation Cytomegalovirus Congenital CMV Viral latency Neurons CD4+ T-cells Hippocampus |
| title | Neuron-restricted cytomegalovirus latency in the central nervous system regulated by CD4+ T-cells and IFN-γ |
| title_full | Neuron-restricted cytomegalovirus latency in the central nervous system regulated by CD4+ T-cells and IFN-γ |
| title_fullStr | Neuron-restricted cytomegalovirus latency in the central nervous system regulated by CD4+ T-cells and IFN-γ |
| title_full_unstemmed | Neuron-restricted cytomegalovirus latency in the central nervous system regulated by CD4+ T-cells and IFN-γ |
| title_short | Neuron-restricted cytomegalovirus latency in the central nervous system regulated by CD4+ T-cells and IFN-γ |
| title_sort | neuron restricted cytomegalovirus latency in the central nervous system regulated by cd4 t cells and ifn γ |
| topic | Cytomegalovirus Congenital CMV Viral latency Neurons CD4+ T-cells Hippocampus |
| url | https://doi.org/10.1186/s12974-025-03422-6 |
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