Dataset Information

Eleutheroside B1 mediates its anti-influenza activity through POLR2A and N-glycosylation.

ABSTRACT: Influenza viruses represent a serious threat to human health. Although our research group has previously demonstrated the antiviral and anti?inflammatory activities of eleutheroside B1, a detailed explanation of the mechanism by which it is effective against the influenza virus remains to be elucidated. In the present study, the transcriptomic responses of influenza A virus?infected lung epithelial cells (A549) treated with eleutheroside B1 were investigated using high?throughput RNA sequencing, and potential targets were identified using a molecular docking technique, reverse transcription?quantitative polymerase chain reaction (RT?qPCR) assay, and DNA methylation analysis. The transcriptomic data revealed that there are 1,871 differentially expressed genes (DEGs) between the cells infected with the influenza virus strain variant PR8, and the cells infected with PR8 and treated with eleutheroside B1. Among the DEGs, RNA polymerase II subunit A (POLR2A; encoding the largest subunit of RNA polymerase II) and mannosidase ? class II member 1 (MAN2A1) were selected from the molecular docking analysis with eleutheroside B1. The docking score of Drosophila melanogaster MAN2A1 (3BVT) was 11.3029, whereas that of POLR2A was 9.0133. The RT?qPCR results demonstrated that the expression levels of host genes (MAN2A2, POLR2A) and viral genes (PA, PB1, PB2, HA) were downregulated following eleutheroside B1 treatment. Bisulfite?sequencing PCR was performed to investigate whether eleutheroside B1 was able to modify the DNA methylation of POLR2A, and the results suggested that the average proportion of methylated CpGs (?222?72 bp) increased significantly following treatment with eleutheroside B1. Taken together, these findings suggested that eleutheroside B1 may affect N?glycan biosynthesis, the chemokine signaling pathway, cytokine?cytokine receptor interaction and, in particular, may target the POLR2A to inhibit the production of influenza virus genes.

SUBMITTER: Yan W

PROVIDER: S-EPMC6192727 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Eleutheroside B1 mediates its anti-influenza activity through POLR2A and N-glycosylation.

Yan Wen W Zheng Chunge C He Jiayang J Zhang Wenjie W Huang Xin-An XA Li Xiong X Wang Yutao Y Wang Xinhua X

International journal of molecular medicine 20180907 5

Influenza viruses represent a serious threat to human health. Although our research group has previously demonstrated the antiviral and anti‑inflammatory activities of eleutheroside B1, a detailed explanation of the mechanism by which it is effective against the influenza virus remains to be elucidated. In the present study, the transcriptomic responses of influenza A virus‑infected lung epithelial cells (A549) treated with eleutheroside B1 were investigated using high‑throughput RNA sequencing, ...[more]

PMID: 30226535

Similar Datasets

Project description:Influenza viruses often pose a serious threat to animals and human health. In an attempt to explore the potential of herbal medicine as a treatment for influenza virus infection, eleutheroside B1, a coumarin compound extracted from herba sarcandrae, was identified, which exhibited antiviral and anti‑inflammatory activities against influenza A virus. In this study, high‑throughput RNA sequencing and isobaric tags for relative and absolute quantification (iTRAQ) assays were performed to determine alterations in the non‑coding RNA (ncRNA) transcriptome and proteomics. Bioinformatics and target prediction analyses were used to decipher the potential roles of altered ncRNAs in the function of eleutheroside B1. Furthermore, long ncRNA (lncRNA) and mRNA co‑expressing networks were constructed to analyze the biological functions by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. The analysis of RNA sequencing data revealed that 5 differentially expressed ncRNAs were upregulated and 3 ncRNAs were downregulated in the A549 cells infected with A/PR8/34/H1N1, with or without eleutheroside B1 treatment (PR8+eleu and PR8, respectively). Nuclear paraspeckle assembly transcript 1 (NEAT1) was differentially expressed between the PR8 and A549 cell groups. GO and KEGG pathway analyses indicated that eleutheroside B1 took advantage of the host cell biological processes and molecular function for its antiviral and anti‑inflammatory activities, as well as for regulating cytokine‑cytokine receptor interaction in the immune system, consistent with previous findings. The results of the iTRAQ assays indicated that L antigen family member 3 (LAGE3) protein, essential for tRNA processing, tRNA metabolic processes and ncRNA processing, was downregulated in the PR8+eleu compared with the PR8 group. In the present study, these comprehensive, large‑scale data analysis enhanced the understanding of multiple aspects of the transcriptome and proteomics that are involved in the antiviral and anti‑inflammatory activities of eleutheroside B1. These findings demonstrate the potential of eleutheroside B1 for use in the prevention and treatment of influenza A virus‑mediated infections.

Dataset Information

Eleutheroside B1 mediates its anti-influenza activity through POLR2A and N-glycosylation.

Publications

Eleutheroside B1 mediates its anti-influenza activity through POLR2A and N-glycosylation.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets