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

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60077344%3A_____%2F25%3A00639446" target="_blank" >RIV/60077344:_____/25:00639446 - isvavai.cz</a>

Alternative codes found

RIV/00216224:14310/25:00144406 RIV/62157124:16170/25:43882860 RIV/00027162:_____/25:N0000091

Result on the web

<a href="https://doi.org/10.1128/jvi.00870-25" target="_blank" >https://doi.org/10.1128/jvi.00870-25</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1128/jvi.00870-25" target="_blank" >10.1128/jvi.00870-25</a>

Result language

angličtina

Original language name

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

Original language description

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.IMPORTANCEAlthough an effective vaccine exists, there is no treatment for those infected by the tick-borne encephalitis virus (TBEV). This study aimed to better understand how the virus's surface proteins influence viral tropism and pathogenicity. We created a chimeric virus with prM and E proteins of TBEV in the genetic background of the low-pathogenic Langat virus (LGTV). The chimeric virus remained low pathogenic, similar to LGTV. Both viruses infected similar brain regions, while TBEV showed a strong preference for the cerebellum and Purkinje cells. This means that other parts of the virus, such as non-structural proteins or NCR, likely decide how the virus behaves in the brain. This study also presents the first cryogenic electron microscopy structure of LGTV, the first whole-brain imaging of TBEV infection in mouse brain, and a new model system to study surface proteins in tick-borne flaviviruses-laying groundwork for future studies on viral tropism, antibody cross-reactivity, and virus-receptor interaction.

Czech name

—

Czech description

—

Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

10607 - Virology

Project

<a href="/en/project/GA23-07160S" target="_blank" >GA23-07160S: Molecular pathogenesis of alimentary infection by tick-borne encephalitis virus.</a><br>

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2025

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Journal of Virology

ISSN

0022-538X

e-ISSN

1098-5514

Volume of the periodical

99

Issue of the periodical within the volume

9

Country of publishing house

US - UNITED STATES

Number of pages

23

Pages from-to

e00870-25

UT code for WoS article

001552231800001

EID of the result in the Scopus database

2-s2.0-105016811768