HEИндивидуална стипендия2023–2024

Viroglimmage · Whole brain visualisation of the neuroinflammatory response during acute neurotropic flavivirus infection and its implications for virus-induced neurodegeneration

„Хоризонт Европа“ — Действия „Мария Склодовска-Кюри“

Период: 2023-01-01 → 2024-12-31
Финансиране от ЕС: 206 888 €
Участници: 1
Схема: HORIZON-TMA-MSCA-PF-EF

Линиите свързват координатора с партньорите.

Накратко на български

Невроинфламаторният отговор на мозъка при инфекции с флавивируси, като например вируса на кърлежния енцефалит, се изследва чрез 3D визуализация на целия орган. Това помага за по-доброто разбиране на патогенезата, което може да съпомогне разработването на ефективни терапии и превантивни мерки.

Този кратък обзор е генериран от изкуствен интелект

Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.

Резултати накратко

Whole brain visualisation of the neuroinflammatory response during acute neurotropic flavivirus infection and its implications for virus-induced neurodegeneration

Flaviviruses are globally distributed pathogens and cause severe illness in millions of people worldwide. Several members of the flavivirus family, as well as many more viruses from other families, are neurotropic, which means that they can infect the central nerve system, including the brain. In Europe and Sweden, tick-borne encephalitis virus (TBEV) is the medically most important flavivirus, which is transmitted by ticks. In most cases infections are asymptomatic but, TBEV can also cause severe encephalitis potentially leading to death. Furthermore, 50% of patients who survive tick-borne encephalitis suffer from chronic neurological complications. Unfortunately, there are currently no antiviral drugs available for TBEV or the other neurotropic flaviviruses and treatment remains limited to supportive and symptomatic care. A big issue is that the viral actions in the brain, which lead to this devastating disease are poorly understood, which largely relies on the lack of suitable imaging technology. Although confocal and electron microscopy have provided invaluable knowledge in infection biology, these microscopic imaging techniques do not qualify to visualize viral actions and consequent pathology at the level of the whole brain. Therefore, we are in desperate need of whole brain imaging techniques, capable of visualizing the course of viral infection and the pathological brain changes that go hand in hand. Such techniques can then improve our understanding od viral pathogenesis and aid the development of effective therapies and preventative measures, thereby lowering mortality and incidence of chronic neurological complications. To be able to study viral actions in the brain and its consequences more accurately, the project aimed to optimize and develop whole brain 3D imaging protocols and validated quantification pipelines to study the link between viral infection, virus-induced neuroinflammation and virus-induced neurodegenerative morbidities.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз

Цел на проекта

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.

Оригинален текст от CORDIS (на английски).

Участници

UMEA UNIVERSITET · UMEAКоординаторШвеция