| Project Detail |
Understanding the link between flavivirus-induced neuroinflammation and neurodegeneration
Neurotropic flaviviruses which include tick-borne encephalitis virus, Japanese encephalitis virus, West Nile virus and Zika virus infect the central nervous system, leading to encephalitis. Survivors are often left with chronic neurological symptoms, associated with neuronal death and immune-related disorders. Funded by the Marie Sklodowska-Curie Actions programme, the Viroglimmage project aims to elucidate the interplay between virus infection, inflammation, neuronal death and the development of neurodegeneration. The study will optimise optical projection tomography and positron emission tomography ex vivo for the quantification of neuroinflammation and tau accumulation. The objective is to investigate the effect of virus-induced neuroinflammation in the course of acute flavivirus infection on the induction of neurodegeneration and tauopathy.
Neurotropic flaviviruses such as tick-borne encephalitis virus (TBEV), Japanese Encephalitis Virus (JEV), West Nile Virus (WNV) and Zika Virus (ZIKV) can enter and infect the central nervous system, potentially leading to lethal encephalitis. Furthermore, survivors often suffer from chronic neurological complications, most likely due to virus-induced neuronal death and immune-related pathology. The past decade, the notion that neurotropic virus infections cause changes to specific neuronal populations, driving accelerated brain ageing and neurodegeneration has become an emerging concept. However, the interplay between virus infection, inflammation, neuronal death and neurodegeneration remains unravelled. In this project, I propose to investigate virus-induced neuroinflammation and its effect on pathways underlying neurodegeneration with frontline imaging techniques. To do so, I will optimise ex vivo optical projection tomography (OPT) and positron emission tomography (PET) for neuroinflammation and tau tangles and develop accurate image-based quantification pipelines for the proposed markers. These will thereafter be applied to study the neuroinflammatory course in acute flavivirus infection and, to unravel the specific role of the microglia in infection and neuroinflammation. Finally, I will investigate the effect of infection and virus-induced neuroinflammation on induction of neurodegeneration, reflected the induction of tauopathy. Taken together, this project will lead to the development of advanced ex vivo imaging techniques to visualise neuroinflammation and virus-induced neurodegeneration and, will improve our understanding on how neurotropic flaviviruses drive the brain into accelerated ageing, thereby priming neurodegeneration. |
