Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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3-anhydro-6-hydroxy-ophiobolin A inhibits the replication of influenza A virus in vitro and in vivo


ABSTRACT: Influenza is a major cause of morbidity and mortality worldwide, and the emerging drug resistance poses an increasing challenge to the treatment of influenza virus infection. Therefore, the development of a novel antiviral drugs has become an urgent task to combat against the influenza viruses that are resistant to the current therapeutic treatment. Here, by screening a small molecule chemical compound library, we identified 3-anhydro-6-epi-ophiobolin A (named L435) as a potent anti-influenza agent. Mechanistically, L435 markedly reduced influenza virus replication in vitro and in vivo. Importantly, L435 treatment improved the survival of influenza-virus-infected mice, suggesting that L435 may be a novel therapeutic agent for treatment of influenza virus infections. This microarray experiment was carried out to explore gene expression changes in influenza-virus-infected A549 cells after L435 treatment, and find out why L435 could inhibit the replication of influenza A virus. Total RNAs were extracted from three different groups of A549 cells that were mock treated, or infected with WSN and treated with DMSO for 12h, or infected with WSN and treated with L435 for 12 h, using TRIzol reagent (Invitrogen, Carlsbad, CA). Three independent experiments were performed. Samples were amplified and labeled using the One-Color Quick Amp Labeling Kit (Agilent p/n 5190-2305).

ORGANISM(S): Homo sapiens

SUBMITTER: xiaojuan chi 

PROVIDER: E-GEOD-58741 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Robust expression of vault RNAs induced by influenza A virus plays a critical role in suppression of PKR-mediated innate immunity.

Li Fang F   Chen Yuhai Y   Zhang Zhaoyuan Z   Ouyang Jing J   Wang Yi Y   Yan Ruoxiang R   Huang Shile S   Gao George Fu GF   Guo Guijie G   Chen Ji-Long JL  

Nucleic acids research 20151020 21


Protein kinase R (PKR) is a vital component of host innate immunity against viral infection. However, the mechanism underlying inactivation of PKR by influenza A virus (IAV) remains elusive. Here, we found that vault RNAs (vtRNAs) were greatly induced in A549 cells and mouse lungs after infection with IAV. The viral NS1 protein was shown to be the inducer triggering the upregulation of vtRNAs. Importantly, silencing vtRNA in A549 cells significantly inhibited IAV replication, whereas overexpressi  ...[more]

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