Department of Biotechnology, University of Chemistry and Technology, 166 28 Prague, Czech Republic.
Institute of Organic Chemistry and Biochemistry Research Centre & Gilead Sciences, Czech Academy of Sciences, 166 10 Prague, Czech Republic.
Proc Natl Acad Sci U S A. 2024 Oct;121(40):e2407990121. doi: 10.1073/pnas.2407990121. Epub 2024 Sep 25.
We explored how a simple retrovirus, Mason-Pfizer monkey virus (M-PMV) to facilitate its replication process, utilizes DHX15, a cellular RNA helicase, typically engaged in RNA processing. Through advanced genetic engineering techniques, we showed that M-PMV recruits DHX15 by mimicking cellular mechanisms, relocating it from the nucleus to the cytoplasm to aid in viral assembly. This interaction is essential for the correct packaging of the viral genome and critical for its infectivity. Our findings offer unique insights into the mechanisms of viral manipulation of host cellular processes, highlighting a sophisticated strategy that viruses employ to leverage cellular machinery for their replication. This study adds valuable knowledge to the understanding of viral-host interactions but also suggests a common evolutionary history between cellular processes and viral mechanisms. This finding opens a unique perspective on the export mechanism of intron-retaining mRNAs in the packaging of viral genetic information and potentially develop ways to stop it.
我们探讨了一种简单的逆转录病毒——猴病毒 40(M-PMV)如何利用其复制过程中利用 DHX15,一种通常参与 RNA 加工的细胞 RNA 解旋酶。通过先进的遗传工程技术,我们表明 M-PMV 通过模拟细胞机制招募 DHX15,将其从细胞核转移到细胞质,以帮助病毒组装。这种相互作用对于正确包装病毒基因组至关重要,对于其感染性也至关重要。我们的发现为病毒操纵宿主细胞过程的机制提供了独特的见解,突出了病毒利用细胞机制进行复制的复杂策略。这项研究增加了对病毒-宿主相互作用的理解,也表明细胞过程和病毒机制之间存在共同的进化历史。这一发现为病毒遗传信息包装中内含子保留 mRNA 的输出机制提供了独特的视角,并为阻止该机制提供了可能的途径。