Understanding viral tropism and neuroinflammation using whole brain imaging
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In our events, we are committed to Aalto University’s principles for a safer space.
Welcome to our ABC Seminars! This seminar series is open for everyone. The talk will take place in Otakaari 1, Room A2 (A215). After the talks, coffee and pulla will be served.
The event will be also streamed via Zoom at: https://aalto.zoom.us/j/67444945844
Title:
Understanding viral tropism and neuroinflammation using whole brain imaging
Abstract:
Neurotropic viral infections can cause severe neurological disease, yet the mechanisms determining viral tropism and the spatial organization of neuroinflammation remain poorly understood. We have developed a whole-brain imaging approach combining tissue clearing, light-sheet fluorescence microscopy (LSFM), and single-cell RNA sequencing to investigate viral distribution and immune responses during tick-borne flavivirus infection.
Using tick-borne encephalitis virus (TBEV) and the closely related, attenuated Langat virus (LGTV), we investigated the contribution of viral entry receptors and structural proteins to neurotropism and pathogenicity. Although LRP8 is an important entry receptor for TBEV, our findings demonstrate that receptor usage alone does not determine viral tropism or pathogenicity in the brain. A chimeric LGTV expressing TBEV structural proteins retained the attenuated phenotype of LGTV, suggesting an important contribution of non-structural viral proteins.
We further applied whole-brain imaging to characterize the spatial relationship between viral infection and neuroinflammation. We identified useful markers for visualizing infiltrating monocytes and macrophages, which progressively acquired a proinflammatory phenotype but remained predominantly associated with blood vessels rather than sites of infection. In contrast, resident microglia underwent progressive activation without preferential accumulation around infected regions.
Together, these findings highlight the complex interplay between viral determinants, cellular tropism, and host immune responses. Our whole-brain imaging platform provides a powerful approach to investigate neuroinvasion and neuroinflammation at single-cell resolution, offering new opportunities to understand the mechanisms underlying viral neuropathogenesis.