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Publications

Journal Article Epublish 4 citations

PubMed: 40158177 DOI: 10.1186/s12974-025-03422-6

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

J Neuroinflammation 22(1):95

Authors: Fran Krstanović, Andrea Mihalić, Ahmad Seyar Rashidi, Katarzyna M Sitnik, Zsolt Ruzsics, Luka Čičin-Šain, Georges M G M Verjans, Stipan Jonjić, Ilija Brizić

Affiliations

  • Center for Proteomics, Faculty of Medicine, University of Rijeka, 51000, Rijeka, Croatia.
  • HerpeslabNL of the Department of Viroscience, Erasmus Medical Center, 3015 GD, Rotterdam, The Netherlands.
  • Department of Biological Sciences and Pathobiology, University of Veterinary Medicine Vienna, Vienna, 1210, Austria.
  • Department of Viral Immunology, Helmholtz Centre for Infection Research, 38124, Braunschweig, Germany.
  • Institute of Virology, Faculty of Medicine, University Medical Center Freiburg, University of Freiburg, 79104 , Freiburg, Germany.
  • Centre for Individualized Infection Medicine, Helmholtz Centre for Infection Research and the Hannover Medical School, 30625, Hannover, Germany.
  • Department of Biomedical Sciences, Croatian Academy of Sciences and Arts, 51000, Rijeka, Croatia.
  • Center for Proteomics, Faculty of Medicine, University of Rijeka, 51000, Rijeka, Croatia.

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.

MeSH

Interferon-Gamma, Cells, Neurons, Cytomegalovirus, Central Nervous System, Herpesviridae, Nervous System, Infections

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