Retroviral G-patch Motif Recruits Cellular DHX15 Helicase to Fascilitate Retroviral RNA Packaging

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60461373%3A22810%2F25%3A43932657" target="_blank" >RIV/60461373:22810/25:43932657 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/60461373:22330/25:43932657

Výsledek na webu

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DOI - Digital Object Identifier

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Jazyk výsledku

angličtina

Název v původním jazyce

Retroviral G-patch Motif Recruits Cellular DHX15 Helicase to Fascilitate Retroviral RNA Packaging

Popis výsledku v původním jazyce

RNA helicases play diverse roles in viral replication cycles. We have discovered a unique mechanism by which the simple retrovirus Mason-Pfizer monkey virus (M-PMV) co-opts the host DEAH-box helicase DHX15 to support its replication. We show that a viral G-patch motif, located within the viral polyproteins, acts as a cofactor for DHX15, mimicking cellular G-patch proteins. This interaction drives the relocalization of DHX15 from the nucleus to the cytoplasm, where it is specifically incorporated into viral particles.Disruption of the G-patch or downregulation of DHX15 severely impairs gRNA packaging and viral infectivity. Using biochemical, structural, and imaging approaches, we demonstrate that the M-PMV G-patch adopts a brace-helix–brace-loop structure, enabling a binding mode analogous to that of cellular G-patch/DHX15 complexes. Notably, PAR-CLIP analysis revealed a DHX15 interaction site close the splice site at the 5´end and upstream of the constitutive transport element (CTE) in the viral gRNA, implicating DHX15 in gRNA splicing, nuclear export and remodeling essential for packaging.These findings reveal a novel role for DHX15 in the retroviral life cycle and highlight the functional versatility of DEAH-box helicases beyond their canonical nuclear roles.This work was funded by the project National Institute of virology and bacteriology (Programme EXCELES, ID Project No. LX22NPO5103) - Funded by the European Union - Next Generation EU.

Název v anglickém jazyce

Retroviral G-patch Motif Recruits Cellular DHX15 Helicase to Fascilitate Retroviral RNA Packaging

Popis výsledku anglicky

RNA helicases play diverse roles in viral replication cycles. We have discovered a unique mechanism by which the simple retrovirus Mason-Pfizer monkey virus (M-PMV) co-opts the host DEAH-box helicase DHX15 to support its replication. We show that a viral G-patch motif, located within the viral polyproteins, acts as a cofactor for DHX15, mimicking cellular G-patch proteins. This interaction drives the relocalization of DHX15 from the nucleus to the cytoplasm, where it is specifically incorporated into viral particles.Disruption of the G-patch or downregulation of DHX15 severely impairs gRNA packaging and viral infectivity. Using biochemical, structural, and imaging approaches, we demonstrate that the M-PMV G-patch adopts a brace-helix–brace-loop structure, enabling a binding mode analogous to that of cellular G-patch/DHX15 complexes. Notably, PAR-CLIP analysis revealed a DHX15 interaction site close the splice site at the 5´end and upstream of the constitutive transport element (CTE) in the viral gRNA, implicating DHX15 in gRNA splicing, nuclear export and remodeling essential for packaging.These findings reveal a novel role for DHX15 in the retroviral life cycle and highlight the functional versatility of DEAH-box helicases beyond their canonical nuclear roles.This work was funded by the project National Institute of virology and bacteriology (Programme EXCELES, ID Project No. LX22NPO5103) - Funded by the European Union - Next Generation EU.

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