Генетическая Вариабельность 5'-Нетранслируемой Области Генома Вируса Клещевого Энцефалита Из Разных Регионов Северной Евразии

Tick-borne encephalitis virus (TBEV) is the aetiological agent of tick-borne encephalitis, an infectious disease of the central nervous system that is often associated with severe sequelae in humans. While TBEV is typically classified into three subtypes, recent evidence suggests a more varied range of TBEV subtypes and lineages that differ substantially in the architecture of their 3ʹ untranslated region (3ʹUTR). Building on comparative genomic approaches and thermodynamic modelling, we characterize the TBEV UTR structureome diversity and propose a unified picture of pervasive non-coding RNA structure conservation. Moreover, we provide an updated phylogeny of TBEV, building on more than 220 publicly available complete genomes, and investigate the molecular epidemiology and phylodynamics with Nextstrain, a web-based visualization framework for real-time pathogen evolution.

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Evolutionary traits of Tick-borne encephalitis virus: Pervasive non-coding RNA structure conservation and molecular epidemiology

Kutschera

Wolfinger

2022

Virus Evolution

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Functional characterization of 5′ untranslated region (UTR) secondary RNA structures in the replication of tick-borne encephalitis virus in mammalian cells

et al. 2023

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Tick-borne Encephalitis Virus (TBEV) is an emerging flavivirus that causes neurological disorders including viral encephalitis of varying severity. Whilst secondary RNA structures within the 5′ untranslated regions (UTRs) of many flaviviruses determine both virus replication and pathogenic outcomes in humans, these elements have not been systematically investigated for TBEV. In this study, we investigated the role of predicted RNA secondary elements of the first 107 nucleotides (nts) of the viral genome forming the stem-loop A (SLA). Experiments were performed in replicons and infectious TBEV system. This region comprises three distinct structures: 5’ stem 0 (S0), stem-loop 1 (SL1) and stem-loop 2 (SL2). S0 was found to be essential for virus infection as mutations in the lower stem of this region significantly reduced virus replication. Point mutations in SL1 that preserved the Y-shape confirmation delayed viral RNA replication but did not abolish virus infectivity. Deletion of SL2 did not abolish infectivity but had a negligible effect on virus propagation. No correlation was observed between in vitro translation efficiency and virus infectivity, suggesting that the 5’UTR functions independently to virus translation. Together, these findings reveal distinct RNA elements within the 5′UTR that are essential for the stability and replication of viral RNA. We further identify changes in RNA folding that lead to altered TBEV infectivity and pathogenesis.

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The comparative genomic analysis provides insights into the phylogeny and virulence of tick-borne encephalitis virus vaccine strain Senzhang

Zhang

Tian

et al. 2022

PLoS ONE

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Tick-borne encephalitis virus (TBEV) is one of the most dangerous tick-borne viral pathogens for humans. It can cause severe tick-borne encephalitis (TBE), multiple neurological complications, and death. The European subtype (TBEV-Eu), Siberian subtype (TBEV-Sib), and Far-Eastern subtype (TBEV-FE) are three main TBEV subtypes, causing varying clinical manifestations. Though TBEV-FE is the most virulent TBEV subtype, the degree of variation in the amino acid sequence of TBEV polyprotein is not high, leaving an issue without proper explanation. We performed phylogenic analysis on 243 TBEV strains and then took Senzhang strain as a query strain and representative strains of three major TBEV subtypes as reference strains to perform the comparative genomic analysis, including synteny analysis, SNP analysis, InDel analysis, and multiple sequence alignment of their envelope (E) proteins. The results demonstrated that insertions or deletions of large fragments occurred at the 3’ end but not at the 5’ end or in the CDS region of TBEV Senzhang strain. In addition, SNP sites are mainly located in the CDS region, with few SNP sites in the non-coding region. Our data highlighted the insertions or deletions of large fragments at the 3’ end and SNP sites in the CDS region as genomic properties of the TBEV Senzhang strain compared to representative strains with the main subtypes. These features are probably related to the virulence of the TBEV Senzhang strain and could be considered in future vaccine development and drug target screening for TBEV.

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Генетическая Вариабельность 5'-Нетранслируемой Области Генома Вируса Клещевого Энцефалита Из Разных Регионов Северной Евразии

Cited by 3 publications

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Evolutionary traits of Tick-borne encephalitis virus: Pervasive non-coding RNA structure conservation and molecular epidemiology

Evolutionary traits of Tick-borne encephalitis virus: Pervasive non-coding RNA structure conservation and molecular epidemiology

Functional characterization of 5′ untranslated region (UTR) secondary RNA structures in the replication of tick-borne encephalitis virus in mammalian cells

The comparative genomic analysis provides insights into the phylogeny and virulence of tick-borne encephalitis virus vaccine strain Senzhang

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