Impact of viral virulence on neuro-invasion and neuro-pathology caused by tick-borne encephalitis virus infections. Einfluss der Virulenz auf die Neuroinvasion und Neuropathology bei TBEV Infektionen.

Viral infection of the nervous system is a rare event, but if a virus is able to enter and to establish an infection the consequences are often severe. The factors controlling viral neuro-invasiveness and neuro-pathogenicity are largely unknown. However, the innate immune response, especially the type I interferon (IFN) response, and the virulence of the virus are very important to control viral infections. We will analyze how TBEV strains of different pathogenicity affect peripheral and brain-specific antiviral response. By infection of C57BL/6 mice we will investigate viral replication and spread. Cytokine, chemokine and interferon response will be determined in the periphery and the central nervous system upon infection. We will investigate differences of cellular tropism upon infection with different virulent virus strains, and how the infection affects induction of innate and adaptive immunity. In addition, brain-region specific antiviral response will be analyzed upon direct infection of the brain to determine the impact on neuropathology. Mice deficient in peripheral or CNS-specific IFN response will give impact, how type I IFN response regulates viral replication and spread, neuro-invasion and neuro-pathology.