Influence of the pre-membrane and envelope proteins on
structure, pathogenicity, and tropism of tick-borne
encephalitis virus.

J 2025

Influence of the pre-membrane and envelope proteins on structure, pathogenicity, and tropism of tick-borne encephalitis virus.

ROSENDAL, Ebba; Kyrylo BISIKALO; Stefanie MA WILLEKENS; Marie LINDGREN; Jiří HOLOUBEK et al.

Základní údaje

Originální název

Influence of the pre-membrane and envelope proteins on structure, pathogenicity, and tropism of tick-borne encephalitis virus.

Autoři

Vydání

Journal of Virology, American Society for Microbiology, 2025, 0022-538X

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10607 Virology

Stát vydavatele

Spojené státy

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 3.800 v roce 2024

Označené pro přenos do RIV

Ano

Kód RIV

RIV/00216224:14310/25:00144406

Organizační jednotka

Přírodovědecká fakulta

Klíčová slova anglicky

tick-borne encephalitis; Langat virus; whole brain imaging; viral pathogenesis; chimera virus; cryo-EM structure

Štítky

14314010, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 13. 11. 2025 15:33, Mgr. Marie Novosadová Šípková, DiS.

Anotace

V originále

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.

Návaznosti

GA23-07160S, projekt VaV

Název: Molekulární patogeneze alimentární infekce virem klíšťové encefalitidy.

Investor: Grantová agentura ČR, Molekulární patogeneze alimentární infekce virem klíšťové encefalitidy.

Citovat

ROSENDAL, Ebba; Kyrylo BISIKALO; Stefanie MA WILLEKENS; Marie LINDGREN; Jiří HOLOUBEK; Pavel SVOBODA; Amanda LAPPALAINEN; Ebba KÖNIGHOFER; Ekaterina MIRGORODSKAYA; Rickard NORDÉN; Federico MORINI; William ROSENBAUM; Daniel RŮŽEK; Ulf AHLGREN; Maria ANASTASINA; Andres MERITS; Sarah J BUTCHER; Emma NILSSON a Anna K ÖVERBY. Influence of the pre-membrane and envelope proteins on structure, pathogenicity, and tropism of tick-borne encephalitis virus. Journal of Virology. American Society for Microbiology, 2025, roč. 99, č. 9, s. "e00870-25", 23 s. ISSN 0022-538X. Dostupné z: https://doi.org/10.1128/jvi.00870-25.

@article{2513072,
   author = {Rosendal, Ebba and Bisikalo, Kyrylo and Willekens, Stefanie MA and Lindgren, Marie and Holoubek, Jiří and Svoboda, Pavel and Lappalainen, Amanda and Könighofer, Ebba and Mirgorodskaya, Ekaterina and Nordén, Rickard and Morini, Federico and Rosenbaum, William and Růžek, Daniel and Ahlgren, Ulf and Anastasina, Maria and Merits, Andres and Butcher, Sarah J and Nilsson, Emma and Överby, Anna K},
   article_number = {9},
   doi = {https://doi.org/10.1128/jvi.00870-25},
   keywords = {tick-borne encephalitis; Langat virus; whole brain imaging; viral pathogenesis; chimera virus; cryo-EM structure},
   language = {eng},
   issn = {0022-538X},
   journal = {Journal of Virology},
   title = {Influence of the pre-membrane and envelope proteins on structure, pathogenicity, and tropism of tick-borne encephalitis virus.},
   url = {https://journals.asm.org/doi/10.1128/jvi.00870-25},
   volume = {99},
   year = {2025}
}

TY  - JOUR
ID  - 2513072
AU  - Rosendal, Ebba - Bisikalo, Kyrylo - Willekens, Stefanie MA - Lindgren, Marie - Holoubek, Jiří - Svoboda, Pavel - Lappalainen, Amanda - Könighofer, Ebba - Mirgorodskaya, Ekaterina - Nordén, Rickard - Morini, Federico - Rosenbaum, William - Růžek, Daniel - Ahlgren, Ulf - Anastasina, Maria - Merits, Andres - Butcher, Sarah J - Nilsson, Emma - Överby, Anna K
PY  - 2025
TI  - Influence of the pre-membrane and envelope proteins on structure, pathogenicity, and tropism of tick-borne encephalitis virus.
JF  - Journal of Virology
VL  - 99
IS  - 9
SP  - "e00870-25"
EP  - "e00870-25"
PB  - American Society for Microbiology
SN  - 0022538X
KW  - tick-borne encephalitis
KW  - Langat virus
KW  - whole brain imaging
KW  - viral pathogenesis
KW  - chimera virus
KW  - cryo-EM structure
UR  - https://journals.asm.org/doi/10.1128/jvi.00870-25
N2  - 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.
ER  -

ROSENDAL, Ebba; Kyrylo BISIKALO; Stefanie MA WILLEKENS; Marie LINDGREN; Jiří HOLOUBEK; Pavel SVOBODA; Amanda LAPPALAINEN; Ebba KÖNIGHOFER; Ekaterina MIRGORODSKAYA; Rickard NORDÉN; Federico MORINI; William ROSENBAUM; Daniel RŮŽEK; Ulf AHLGREN; Maria ANASTASINA; Andres MERITS; Sarah J BUTCHER; Emma NILSSON a Anna K ÖVERBY. Influence of the pre-membrane and envelope proteins on structure, pathogenicity, and tropism of tick-borne encephalitis virus. \textit{Journal of Virology}. American Society for Microbiology, 2025, roč.~99, č.~9, s.~''e00870-25'', 23 s. ISSN~0022-538X. Dostupné z: https://doi.org/10.1128/jvi.00870-25.

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