MASON-PFIZER MONKEY VIRUS RECRUITS DHX15 TO PROMOTE RNA PACKAGING

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60461373%3A22810%2F25%3A43932631" target="_blank" >RIV/60461373:22810/25:43932631 - isvavai.cz</a>

Alternative codes found

RIV/60461373:22330/25:43932631

Result on the web

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DOI - Digital Object Identifier

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Result language

angličtina

Original language name

MASON-PFIZER MONKEY VIRUS RECRUITS DHX15 TO PROMOTE RNA PACKAGING

Original language description

The DHX15 is an RNA helicase that plays a pivotal role in various steps of cellular RNA metabolism. Its activity and substrate specificity are modulated by protein cofactors, especially those containing glycine-rich sequence known as the G-patch domain (GPD)1. While this regulatory mechanism has been well-characterised in the context of cellular processes, recent studies have revealed that certain viruses have evolved to utilise this mechanism for their own benefit. A specific example is Mason-Pfizer monkey virus (M-PMV), a betaretrovirus in which GPD has been identified. The sequence and secondary structure of this viral GPD resemble cellular ones known to activate DHX15 (e. g. NF-kappa-B-repressing factor) suggesting a shared mode of action.Using PAR-CLIP analysis, constitutive transport element, an RNA element crucial for the export of unspliced viral RNA from the nucleus, and its upstream sequence were identified as potential binding site of DHX15 in M-PMV genome2. In order to confirm and also narrow the DHX15 binding site, side-directed mutagenesis of this region was performed and the interaction was studied in vitro using microscale thermophoresis. Simultaneously, the impact of the mutations on M-PMV life cycle was investigated.The overall results confirm the binding site position for DHX15 in the M-PMV genome. Mutagenesis of the binding site led to substantially decreased level of DHX15 in purified viral particles, accompanied by reduced levels of viral RNA.These findings reveal a previously uncharacterized mechanism by which M-PMV manipulates host RNA helicase activity to optimize its replication strategy. This work not only expands our understanding of host–virus interactions at the molecular level but also opens new avenues for exploring helicase-mediated control of RNA fate in retroviral life cycles.

Czech name

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Czech description

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Type

O - Miscellaneous

CEP classification

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OECD FORD branch

10607 - Virology

Project

<a href="/en/project/LX22NPO5103" target="_blank" >LX22NPO5103: National Institute of Virology and Bacteriology</a><br>

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>S - Specificky vyzkum na vysokych skolach

Publication year

2025

Confidentiality

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