Background: Respiratory syncytial virus (RSV) is the second leading cause of death due to lower respiratory tract infections. Effective prevention and treatment measures are lacking, posing a huge socioeconomic burden to the world. -methyladenosine (mA) is the most common internal modification in messenger RNA and noncoding RNA. Numerous recent studies have shown that the dysregulation of mA modification is associated with diseases caused by pathogenic viruses.
Methods: The changes in mA modification were evaluated using mA RNA methylation assay. The differences in gene expression levels of various mA-modifying enzymes were observed using Quantitative Real-time PCR (qRT-PCR) during RSV infection. The autophagosomes were observed using transmission electron microscopy, and the expression of autophagy-associated protein Microtubule Associated Protein 1 Light Chain 3 Beta Ⅱ/Ⅰ (LC3B Ⅱ/Ⅰ) and Beclin1 in Human Normal Lung Epithelial Cells (BEAS-2B) cells using Western blot during RSV infection. The significantly differentially expressed genes were screened guided by bioinformatics. Their relationship with mA-modifying enzymes was analyzed through protein-protein interaction network and expression correlation analysis.
Results: The mA abundance decreased and demethylase Fat Mass and Obesity- Associated Protein (FTO) significantly increased during RSV infection after 24 h. We also found that the DNA Damage-Inducible Transcript 3 Protein (DDIT3) level significantly increased during RSV infection after 24 h and observed autophagosomes in BEAS-2B cells. In addition, RSV infection could cause the upregulation of LC3B Ⅱ/Ⅰ and Beclin1. The expression correlation analysis showed that DDIT3 levels were positively correlated with the FTO level, and Methyltransferase Like 3 (METTL3), RNA Binding Motif Protein 15B (RBM15B), YTH Domain-Containing Family Protein 1 (YTHDF1), and levels were negatively correlated with the DDIT3 level.
Conclusions: We uncovered a significant role for mA modification during RSV infection. Also, a correlation was found between mA and autophagy, providing new ideas for therapeutic advancements in RSV treatment.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10114233 | PMC |
| http://dx.doi.org/10.1016/j.heliyon.2023.e15307 | DOI Listing |
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