STRUCTURAL AND MECHANISTIC INSIGHTS INTO REPLICATION OF RIFT VALLEY FEVER VIRUS

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14740%2F25%3A00142758" target="_blank" >RIV/00216224:14740/25:00142758 - isvavai.cz</a>

Výsledek na webu

<a href="https://nivb.cz/en/2025/10/29/nivb-meeting-2025/" target="_blank" >https://nivb.cz/en/2025/10/29/nivb-meeting-2025/</a>

DOI - Digital Object Identifier

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Jazyk výsledku

angličtina

Název v původním jazyce

STRUCTURAL AND MECHANISTIC INSIGHTS INTO REPLICATION OF RIFT VALLEY FEVER VIRUS

Popis výsledku v původním jazyce

Rift Valley fever virus (RVFV) is a segmented, zoonotic RNA virus that causes severe disease in both humans and livestock. In newborn animals, mortality rates can approach 100%, while in humans, severe hemorrhagic forms carry fatality rates of up to 50%. Central to RVFV replication and transcription is the viral RNA-dependent RNA polymerase (L-protein), which initiates RNA synthesis through a distinctive prime-and-realign mechanism directed by promoter sequences at the 5′ and 3′ termini of each genomic segment. While this strategy is essential for viral propagation, the structural and mechanistic basis for promoter-driven regulation of RVFV replication has remained poorly understood. Here, we applied single-particle cryo-electron microscopy to visualise the RVFV L-protein engaged with promoter sets during replication. Our structures capture distinct conformational intermediates and reveal how promoter binding modulates the architecture of functional domains, stabilising specific states along the replication pathway. These findings provide a mechanistic framework for understanding promoter-dependent control of viral RNA synthesis and identify structural features of the L-protein that could be targeted for antiviral intervention.

Název v anglickém jazyce

STRUCTURAL AND MECHANISTIC INSIGHTS INTO REPLICATION OF RIFT VALLEY FEVER VIRUS

Popis výsledku anglicky

Rift Valley fever virus (RVFV) is a segmented, zoonotic RNA virus that causes severe disease in both humans and livestock. In newborn animals, mortality rates can approach 100%, while in humans, severe hemorrhagic forms carry fatality rates of up to 50%. Central to RVFV replication and transcription is the viral RNA-dependent RNA polymerase (L-protein), which initiates RNA synthesis through a distinctive prime-and-realign mechanism directed by promoter sequences at the 5′ and 3′ termini of each genomic segment. While this strategy is essential for viral propagation, the structural and mechanistic basis for promoter-driven regulation of RVFV replication has remained poorly understood. Here, we applied single-particle cryo-electron microscopy to visualise the RVFV L-protein engaged with promoter sets during replication. Our structures capture distinct conformational intermediates and reveal how promoter binding modulates the architecture of functional domains, stabilising specific states along the replication pathway. These findings provide a mechanistic framework for understanding promoter-dependent control of viral RNA synthesis and identify structural features of the L-protein that could be targeted for antiviral intervention.

Druh

O - Ostatní výsledky

CEP obor

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OECD FORD obor

10607 - Virology

Projekt

<a href="/cs/project/LX22NPO5103" target="_blank" >LX22NPO5103: Národní institut virologie a bakteriologie</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2025

Kód důvěrnosti údajů

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