Latentna infekcija citomegalovirusom u središnjem živčanom sustavu
Description: Many viruses can cause persistent or latent infections and/or inflammation in the CNS. Growing body of evidence suggests that such infections can cause wide array of pathologies and morbidities. Congenital cytomegalovirus (CMV) infection is a major cause of trans-placentally transmitted congenital infections and may cause a wide range of structural and functional disabilities and permanent neurological sequelae. Our preliminary data obtained using in vivo mouse model of congenital CMV infection shows that neurons are site of latent mouse (M)CMV infection and reactivation, while astrocytes and microglia do not carry latent virus. Latent MCMV infection in the CNS is associated with life-long retention of tissue-resident T cells which are required to control latent virus. Furthermore, we found that microglia is persistently activated in the latently infected CNS. It is not known which T cell mechanisms are required to control latent infection in neurons and how persistent activation of microglia contributes to these processes. In addition, the ability of virus reactivating in neurons to spread to other cells is not known. Here we will answer these questions. To assess if virus reactivating in neurons can spread to other cells we will cocultivate latently infected neurons with MCMV-susceptible cells, and use organotypic tissue culture model. To determine the role of activated microglia in control of latent virus, we will use microglia depletion approaches, as well as inducible conditional knockout mice to selectively eliminate key effector molecules of microglia. Finally, we will investigate brain structural and functional changes caused by latent CMV infection in the brain during aging. Understanding mechanisms of CNS damage and deciphering the mechanisms of latent infection, as well as associated immune response is crucial to develop better interventional therapy. In addition, this study will open new avenues of research of latent viral infections in brain.
Funder: Hrvatska Zaklada za Znanost
Amount: €72
Funding type: grant
Funder scheme: DOK
Start date: 2026-02-01
End date: 2032-01-31
Investigator: Ilija Brizić
Institution: University of Rijeka, Faculty of Medicine
Funded outputs count: 0
Funder award ID: DOK-2025-02-6667
OpenAlex ID: G4133577303