SARS-CoV-2 Nsp13 helicase modulates miR-146a-mediated signaling pathways

IF 2.8 3区医学 Q3 VIROLOGY

Virology Pub Date : 2025-03-07 DOI:10.1016/j.virol.2025.110493

Eryn Lundrigan , Spencer Uguccioni , Christine Hum , Nadine Ahmed , John Paul Pezacki

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引用次数: 0

Abstract

Despite the successful development of vaccines and antiviral therapeutics against SARS-CoV-2, its tendency to mutate rapidly has emphasized the need for continued research to better understand this virus’s mechanism of pathogenesis and interactions with host signaling pathways. In this study, we sought to explore how the SARS-CoV-2 non-structural protein 13 (Nsp13) helicase, a highly conserved coronavirus protein that is essential for viral replication, influences host biological and cellular processes. Global transcriptomic analyses of Nsp13-transfected A549 cells identified changes in pathways involved in post-transcriptional gene silencing and translational repression by RNA, such as microRNAs (miRNAs). Upon further bioinformatic analyses, we identified miR-146a-mediated signaling pathways to be of interest as this miRNA has been previously linked to the regulation of host inflammation and innate immune responses. We found that miR-146a was induced in Nsp13-transfected cells and observed a corresponding decrease in the gene expression of two miR-146a targets, TRAF6 and IRAK1, which are important upstream regulators of NF-kB activation and IFN signaling. These results suggest that Nsp13-induced miR-146a signaling cascades, namely NF-kB activation and SMAD4 signaling, may provide valuable insight for the development of novel antiviral therapeutics against COVID-19 variants.

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来源期刊

Virology 医学-病毒学

CiteScore

6.00

自引率

0.00%

发文量

157

审稿时长

50 days

期刊介绍： Launched in 1955, Virology is a broad and inclusive journal that welcomes submissions on all aspects of virology including plant, animal, microbial and human viruses. The journal publishes basic research as well as pre-clinical and clinical studies of vaccines, anti-viral drugs and their development, anti-viral therapies, and computational studies of virus infections. Any submission that is of broad interest to the community of virologists/vaccinologists and reporting scientifically accurate and valuable research will be considered for publication, including negative findings and multidisciplinary work.Virology is open to reviews, research manuscripts, short communication, registered reports as well as follow-up manuscripts.