Influence of the pre-membrane and envelope proteins on structure, pathogenicity, and tropism of tick-borne encephalitis virus.
| Autoři | |
|---|---|
| Rok publikování | 2025 |
| Druh | Článek v odborném periodiku |
| Časopis / Zdroj | Journal of Virology |
| Fakulta / Pracoviště MU | |
| Citace | |
| www | https://journals.asm.org/doi/10.1128/jvi.00870-25 |
| Doi | https://doi.org/10.1128/jvi.00870-25 |
| Klíčová slova | tick-borne encephalitis; Langat virus; whole brain imaging; viral pathogenesis; chimera virus; cryo-EM structure |
| Popis | Tick-borne encephalitis virus (TBEV) is a neurotropic flavivirus that causes thousands of human infections annually. Viral tropism in the brain is determined by the presence of necessary receptors, entry factors, and the ability of the virus to overcome host defenses. The viral structural proteins, pre-membrane (prM), and envelope (E) play an important role in receptor binding, membrane fusion, particle maturation, and antibody neutralization. To understand how these proteins influence virus distribution and tropism in the brain, we generated a chimeric virus harboring the prM and ectodomain of E from TBEV in the background of the low-pathogenic Langat virus (LGTV). We solved the atomic structures of both the chimeric virus and LGTV to compare them to the known TBEV structure. We show that this chimeric virus remains low-pathogenic, while being structurally and antigenically similar to TBEV. Using 3D optical whole brain imaging combined with immunohistochemistry, we found that both LGTV and the chimeric virus primarily infect the cerebral cortex, with no significant differences in their localization or tropism. In contrast, TBEV shows high infection of the cerebellum and a strong preference toward Purkinje cells, indicating that factors other than the prM and E proteins are important for determining TBEV tropism in the brain. Together, this provides new insights into the roles of the structural and non-structural proteins of tick-borne flaviviruses. |
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