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<sup>+</sup> 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<sup>+</sup> 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.

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Publication Details

Journal
Journal of Neuroinflammation
Published
2025-03-29
DOI
https://doi.org/10.1186/s12974-025-03422-6
Citations
4
Primary Topic
Cytomegalovirus and herpesvirus research
Type
article
Field-Weighted Citation Impact
5.42

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article

Neuron-restricted cytomegalovirus latency in the central nervous system regulated by CD4+ T-cells and IFN-γ

Zsolt Ruzsics, Katarzyna Sitnik, Fran Krstanović, Ahmad Rashidi et al.
4 citations
Journal of Neuroinflammation
Cytomegalovirus and herpesvirus research
5.42
article

Neuron-restricted cytomegalovirus latency in the central nervous system regulated by CD4+ T-cells and IFN-γ

Zsolt Ruzsics, Katarzyna Sitnik, Fran Krstanović, Ahmad Rashidi, Stipan Jonjić, Georges M. G. M. Verjans, Ilija Brizić, Andrea Mihalić, Luka Čičin‐Šain
article en
4 citations

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<sup>+</sup> 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<sup>+</sup> 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.

Journal of NeuroinflammationVol. 22(1)
Croatian Academy of Sciences and Arts (HR), University of Veterinary Medicine Vienna (AT), University of Rijeka (HR), University of Freiburg (DE), University Medical Center Freiburg (DE), Helmholtz Centre for Infection Research (DE), Centre for Individualised Infection Medicine (DE), Erasmus University Rotterdam (NL)
European Commission, Deutsche Forschungsgemeinschaft, Lundbeckfonden, Hrvatska Zaklada za Znanost, H. Lundbeck A/S, Horizon 2020 Framework Programme, European Regional Development Fund
Good health and well-being
Openalex Percentile: Top 5%
Cytomegalovirus and herpesvirus research
5.42
DOIOpen Access PDFOpenAlex
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