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.
