Latent CMV in the brain: a hidden threat or adaptation?
Project title: UNIRI PROJECTS BY YOUNG RESEARCHERS AND RESEARCHERS RETURNEES - Latent CMV in the brain: a hidden threat or adaptation?
Funding source: University of Rijeka
Project code: uniri-mz-25-32
Coordinator: Fran Krstanović, PhD
Total funding: 22.665,65 €
Project implementation period: 01.10.2025. - 30.04.2028.
Brief description: All human herpesviruses enter a latent state after the resolution of primary infection. While alpha-herpesviruses, such as herpes simplex virus 1 (HSV-1) and varicella-zoster virus (VZV) establish latency in neurons, other herpesviruses have not been reported to maintain latency in neurons. Recent studies have linked herpesvirus infections to neurological and neuropsychiatric disorders, with HSV-1 being considered a risk factor for Alzheimer's disease (AD), and epidemiological and mechanistic evidence suggesting a causal relationship between Epstein-Barr virus (EBV) and the development of multiple sclerosis (MS). The rising incidence of neurocognitive and neuropsychiatric diseases, along with their significant socioeconomic burden, underscores the need for a deeper understanding of viral latency in the central nervous system (CNS).
Human cytomegalovirus (HCMV) is a leading cause of congenital viral infections, often causing permanent damage to the nervous system in children. Due to its strict species specificity, the pathogenesis of HCMV cannot be directly investigated in animal models. Using a mouse model of congenital CMV (cHCMV) infection, we have shown that after the resolution of the acute phase of infection, murine cytomegalovirus (MCMV) establishes lifelong latency in neurons of the CNS. Limited human studies have shown that the HCMV genome can be detected in the brains of healthy adults above the expected level, while HCMV is also associated with worsening neurocognitive and neuropsychiatric health and is present in patients with glioblastoma multiforme. However, the consequences of latent CMV infection in neurons remain unknown. Therefore, this project aims to investigate the consequences of latent viral infection in neurons at the level of gene expression using a mouse model of cHCMV infection, recombinant reporter virus, transgenic mice, advanced “RiboTag” technology, and translatome sequencing. As part of the project, the implementation of new technologies will be carried out in collaboration with collaborators from Hannover (Prof. Urlich Kalinke, TWINCORE).
