Abstract
Objectives: Ganoderic acid Me [GA-Me], a major bioactive triterpene extracted from Ganoderma lucidum, is often used to treat immune system diseases caused by viral infections. Although triterpenes have been widely employed in traditional medicine, the comprehensive mechanisms by which GA-Me acts against viral infections have not been reported. Sendai virus [SeV]-infected host cells have been widely employed as an RNA viral model to elucidate the mechanisms of viral infection.
Methods: In this study, SeV- and mock-infected [Control] cells were treated with or without 54.3 μM GA-Me. RNA-Seq was performed to identify differentially expressed mRNAs, followed by qRT-PCR validation for selected genes. GO and KEGG analyses were applied to investigate potential mechanisms and critical pathways associated with these genes.
Results: GA-Me altered the levels of certain genes’ mRNA, these genes revealed are associated pathways related to immune processes, including antigen processing and presentation in SeV-infected cells. Multiple signaling pathways, such as the mTOR pathway, chemokine signaling pathway, and the p53 pathways, significantly correlate with GA-Me activity against the SeV infection process. qRT-PCR results were consistent with the trend of RNA-Seq findings. Moreover, PPI network analysis identified 20 crucial target proteins, including MTOR, CDKN2A, MDM2, RPL4, RPS6, CREBBP, UBC, UBB, and NEDD8. GA-Me significantly changed transcriptome-wide mRNA profiles of RNA polymerase II/III, protein posttranslational and immune signaling pathways.
Conclusion: These results should be further assessed to determine the innate immune response against SeV infection, which might help in elucidating the functions of these genes affected by GA-Me treatment in virus-infected cells, including cells infected with SARS-CoV-2.
Keywords: Ganoderic acid Me, Transcriptomic profiling, Sendai virus, RNA virus, SARS-CoV-2
Graphical Abstract
[http://dx.doi.org/10.1186/s13643-019-1218-y] [PMID: 31796121]
[http://dx.doi.org/10.1001/jama.2020.6019] [PMID: 32282022]
[http://dx.doi.org/10.1016/j.phrs.2020.104761] [PMID: 32205232]
[http://dx.doi.org/10.1111/jcmm.13613] [PMID: 29691994]
[http://dx.doi.org/10.1007/s10529-006-9007-9] [PMID: 16786250]
[http://dx.doi.org/10.1016/j.intimp.2007.02.006] [PMID: 17466920]
[http://dx.doi.org/10.1159/000326915] [PMID: 21454974]
[http://dx.doi.org/10.1016/S1734-1140(10)70252-8] [PMID: 20360625]
[http://dx.doi.org/10.1016/j.phymed.2011.01.011] [PMID: 21353507]
[http://dx.doi.org/10.1038/s41598-019-55723-5] [PMID: 31836806]
[http://dx.doi.org/10.1016/j.bbrc.2014.05.019] [PMID: 24845570]
[http://dx.doi.org/10.1615/IntJMedMushrooms.v16.i6.70] [PMID: 25404222]
[http://dx.doi.org/10.6026/97320630007413] [PMID: 22347784]
[http://dx.doi.org/10.1007/s12011-011-8986-0] [PMID: 21301988]
[http://dx.doi.org/10.1038/s41467-020-15562-9] [PMID: 32221306]
[http://dx.doi.org/10.1159/000489832] [PMID: 30016790]
[http://dx.doi.org/10.1038/s41598-018-35231-8] [PMID: 30429577]
[http://dx.doi.org/10.1016/j.intimp.2014.08.001] [PMID: 25138378]
[http://dx.doi.org/10.1038/d41573-020-00016-0] [PMID: 32127666]
[http://dx.doi.org/10.1016/j.chom.2020.02.001] [PMID: 32035028]
[http://dx.doi.org/10.4049/jimmunol.1601194] [PMID: 28011935]
[http://dx.doi.org/10.4161/cc.3.8.1016] [PMID: 15254403]
[http://dx.doi.org/10.1254/jphs.SC0080019] [PMID: 18946196]
[http://dx.doi.org/10.1016/j.antiviral.2020.104872] [PMID: 32768412]
[http://dx.doi.org/10.1007/s00432-020-03287-7] [PMID: 32556504]
[http://dx.doi.org/10.21203/rs.3.rs-544240/v1]
[http://dx.doi.org/10.1016/j.febslet.2007.04.070] [PMID: 17499246]
[http://dx.doi.org/10.3390/v8050124] [PMID: 27187445]
[http://dx.doi.org/10.1007/s42770-018-0021-6] [PMID: 30637656]
[http://dx.doi.org/10.1007/BF01977473] [PMID: 6208021]
[http://dx.doi.org/10.1016/j.coviro.2011.10.008] [PMID: 22328912]
[http://dx.doi.org/10.1186/s12920-018-0335-0] [PMID: 29475453]
[http://dx.doi.org/10.1038/nchembio.476] [PMID: 21076398]
[http://dx.doi.org/10.1007/s10067-016-3496-2] [PMID: 27988812]
[http://dx.doi.org/10.1186/s12906-019-2469-9] [PMID: 30871515]
[http://dx.doi.org/10.1159/000087104] [PMID: 16166805]
[http://dx.doi.org/10.1016/j.antiviral.2020.104902] [PMID: 32739404]
[PMID: 29749430]
[http://dx.doi.org/10.1186/s12917-019-1897-6] [PMID: 31101113]
[http://dx.doi.org/10.3390/cells8080849] [PMID: 31394830]
[http://dx.doi.org/10.3389/fmicb.2020.01630] [PMID: 32765462]
[http://dx.doi.org/10.3389/fphar.2019.01136] [PMID: 31632275]
[http://dx.doi.org/10.1002/pmic.201400586] [PMID: 25764225]
[http://dx.doi.org/10.1016/j.genrep.2020.100765] [PMID: 32835132]
[http://dx.doi.org/10.1080/22221751.2020.1799723] [PMID: 32691695]
[http://dx.doi.org/10.1016/j.cell.2020.04.035] [PMID: 32413319]