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Current Bioinformatics

Editor-in-Chief

ISSN (Print): 1574-8936
ISSN (Online): 2212-392X

Research Article

Transcriptomic Profiling of Ganoderic Acid Me-Mediated Prevention of Sendai Virus Infection

Author(s): Guoqing Wan, Zheyu Fan, Dan-Dan Zhai, Liying Jiang, Shengli Xia, Xuefeng Gu, Changlian Lu, Ping Shi, Xiaobin Zeng, Jihong Meng* and Nianhong Chen*

Volume 17, Issue 7, 2022

Published on: 26 August, 2022

Page: [586 - 598] Pages: 13

DOI: 10.2174/1574893617666220426134011

Price: $65

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, qRT-PCR.

Graphical Abstract
[1]
Zhang X, Aixinjueluo QY, Li SY, et al. Reporting quality of Cochrane systematic reviews with Chinese herbal medicines. Syst Rev 2019; 8(1): 302.
[http://dx.doi.org/10.1186/s13643-019-1218-y] [PMID: 31796121]
[2]
Sanders JM, Monogue ML, Jodlowski TZ, Cutrell JB. Pharmacologic treatments for coronavirus disease 2019 (COVID-19): A review. JAMA 2020; 323(18): 1824-36.
[http://dx.doi.org/10.1001/jama.2020.6019] [PMID: 32282022]
[3]
Runfeng L, Yunlong H, Jicheng H, et al. Lianhuaqingwen exerts anti-viral and anti-inflammatory activity against novel coronavirus (SARS-CoV-2). Pharmacol Res 2020; 156: 104761.
[http://dx.doi.org/10.1016/j.phrs.2020.104761] [PMID: 32205232]
[4]
Zeng P, Guo Z, Zeng X, et al. Chemical, biochemical, preclinical and clinical studies of Ganoderma lucidum polysaccharide as an approved drug for treating myopathy and other diseases in China. J Cell Mol Med 2018; 22(7): 3278-97.
[http://dx.doi.org/10.1111/jcmm.13613] [PMID: 29691994]
[5]
Li YQ, Wang SF. Anti-hepatitis B activities of ganoderic acid from Ganoderma lucidum. Biotechnol Lett 2006; 28(11): 837-41.
[http://dx.doi.org/10.1007/s10529-006-9007-9] [PMID: 16786250]
[6]
Wang G, Zhao J, Liu J, Huang Y, Zhong JJ, Tang W. Enhancement of IL-2 and IFN-gamma expression and NK cells activity involved in the anti-tumor effect of ganoderic acid Me in vivo. Int Immunopharmacol 2007; 7(6): 864-70.
[http://dx.doi.org/10.1016/j.intimp.2007.02.006] [PMID: 17466920]
[7]
Sun JG, Chen CY, Luo KW, et al. 3,5-Dimethyl-H-furo[3,2-g]chromen-7-one as a potential anticancer drug by inducing p53-dependent apoptosis in human hepatoma HepG2 cells. Chemotherapy 2011; 57(2): 162-72.
[http://dx.doi.org/10.1159/000326915] [PMID: 21454974]
[8]
Chen NH, Liu JW, Zhong JJ. Ganoderic acid T inhibits tumor invasion in vitro and in vivo through inhibition of MMP expression. Pharmacol Rep 2010; 62(1): 150-63.
[http://dx.doi.org/10.1016/S1734-1140(10)70252-8] [PMID: 20360625]
[9]
Chen NH, Zhong JJ. p53 is important for the anti-invasion of ganoderic acid T in human carcinoma cells. Phytomedicine 2011; 18(8-9): 719-25.
[http://dx.doi.org/10.1016/j.phymed.2011.01.011] [PMID: 21353507]
[10]
Bharadwaj S, Lee KE, Dwivedi VD, et al. Discovery of Ganoderma lucidum triterpenoids as potential inhibitors against Dengue virus NS2B-NS3 protease. Sci Rep 2019; 9(1): 19059.
[http://dx.doi.org/10.1038/s41598-019-55723-5] [PMID: 31836806]
[11]
Zhang W, Tao J, Yang X, et al. Antiviral effects of two Ganoderma lucidum triterpenoids against enterovirus 71 infection. Biochem Biophys Res Commun 2014; 449(3): 307-12.
[http://dx.doi.org/10.1016/j.bbrc.2014.05.019] [PMID: 24845570]
[12]
Shamaki BU, Sandabe UK, Ogbe AO, Abdulrahman FI, El-Yuguda AD. Methanolic soluble fractions of lingzhi or reishi medicinal mushroom, Ganoderma lucidum (higher Basidiomycetes) extract inhibit neuraminidase activity in Newcastle disease virus (LaSota). Int J Med Mushrooms 2014; 16(6): 579-83.
[http://dx.doi.org/10.1615/IntJMedMushrooms.v16.i6.70] [PMID: 25404222]
[13]
Akbar R, Yam WK. Interaction of ganoderic acid on HIV related target: Molecular docking studies. Bioinformation 2011; 7(8): 413-7.
[http://dx.doi.org/10.6026/97320630007413] [PMID: 22347784]
[14]
Wang L, Hou Y. Determination of trace elements in anti-influenza virus mushrooms. Biol Trace Elem Res 2011; 143(3): 1799-807.
[http://dx.doi.org/10.1007/s12011-011-8986-0] [PMID: 21301988]
[15]
Ou X, Liu Y, Lei X, et al. Characterization of spike glycoprotein of SARS-CoV-2 on virus entry and its immune cross-reactivity with SARS-CoV. Nat Commun 2020; 11(1): 1620.
[http://dx.doi.org/10.1038/s41467-020-15562-9] [PMID: 32221306]
[16]
Gao X, Chen D, Hu X, et al. PLA1A participates in the antiviral innate immune response by facilitating the recruitment of TANK-binding kinase 1 to mitochondria. J Innate Immun 2018; 10(4): 315-27.
[http://dx.doi.org/10.1159/000489832] [PMID: 30016790]
[17]
Mandhana R, Horvath CM. Sendai virus infection induces expression of novel RNAs in human cells. Sci Rep 2018; 8(1): 16815.
[http://dx.doi.org/10.1038/s41598-018-35231-8] [PMID: 30429577]
[18]
Que Z, Zou F, Zhang A, et al. Ganoderic acid Me induces the apoptosis of competent T cells and increases the proportion of Treg cells through enhancing the expression and activation of indoleamine 2,3-dioxygenase in mouse lewis lung cancer cells. Int Immunopharmacol 2014; 23(1): 192-204.
[http://dx.doi.org/10.1016/j.intimp.2014.08.001] [PMID: 25138378]
[19]
Li G, De Clercq E. Therapeutic options for the 2019 novel coronavirus (2019-nCoV). Nat Rev Drug Discov 2020; 19(3): 149-50.
[http://dx.doi.org/10.1038/d41573-020-00016-0] [PMID: 32127666]
[20]
Wu A, Peng Y, Huang B, et al. Genome composition and divergence of the novel coronavirus (2019-nCoV) originating in China. Cell Host Microbe 2020; 27(3): 325-8.
[http://dx.doi.org/10.1016/j.chom.2020.02.001] [PMID: 32035028]
[21]
Ju LG, Zhu Y, Lei PJ, et al. TTLL12 inhibits the activation of cellular antiviral signaling through interaction with VISA/MAVS. J Immunol 2017; 198(3): 1274-84.
[http://dx.doi.org/10.4049/jimmunol.1601194] [PMID: 28011935]
[22]
Huang S, Qu LK, Koromilas AE. Induction of p53-dependent apoptosis in HCT116 tumor cells by RNA viruses and possible implications in virus-mediated oncolysis. Cell Cycle 2004; 3(8): 1043-5.
[http://dx.doi.org/10.4161/cc.3.8.1016] [PMID: 15254403]
[23]
Chen NH, Liu JW, Zhong JJ. Ganoderic acid Me inhibits tumor invasion through down-regulating matrix metalloproteinases 2/9 gene expression. J Pharmacol Sci 2008; 108(2): 212-6.
[http://dx.doi.org/10.1254/jphs.SC0080019] [PMID: 18946196]
[24]
Salmona M, Feghoul L, Mercier-Delarue S, et al. Effect of brincidofovir on adenovirus and A549 cells transcriptome profiles. Antiviral Res 2020; 182: 104872.
[http://dx.doi.org/10.1016/j.antiviral.2020.104872] [PMID: 32768412]
[25]
Liu J, Yang X, Zhang L, et al. Microarray analysis of the expression profile of immune-related gene in rapid recurrence early-stage lung adenocarcinoma. J Cancer Res Clin Oncol 2020; 146(9): 2299-310.
[http://dx.doi.org/10.1007/s00432-020-03287-7] [PMID: 32556504]
[26]
Hazan G, Eubanks A, Gierasch C, et al. Aging regulates post-viral asthmatic airway pathology. 2021.
[http://dx.doi.org/10.21203/rs.3.rs-544240/v1]
[27]
Olivari S, Molinari M. Glycoprotein folding and the role of EDEM1, EDEM2 and EDEM3 in degradation of folding-defective glycoproteins. FEBS Lett 2007; 581(19): 3658-64.
[http://dx.doi.org/10.1016/j.febslet.2007.04.070] [PMID: 17499246]
[28]
Cervantes-Ortiz SL, Zamorano Cuervo N, Grandvaux N. Respiratory syncytial virus and cellular stress responses: Impact on replication and physiopathology. Viruses 2016; 8(5): 124.
[http://dx.doi.org/10.3390/v8050124] [PMID: 27187445]
[29]
Wei W, Kong W. Identification of key genes and signaling pathways during Sendai virus infection in vitro. Braz J Microbiol 2019; 50(1): 13-22.
[http://dx.doi.org/10.1007/s42770-018-0021-6] [PMID: 30637656]
[30]
Higgins PG. Interferons and viral infections. Eur J Clin Microbiol 1984; 3(4): 282-4.
[http://dx.doi.org/10.1007/BF01977473] [PMID: 6208021]
[31]
Schoggins JW, Rice CM. Interferon-stimulated genes and their antiviral effector functions. Curr Opin Virol 2011; 1(6): 519-25.
[http://dx.doi.org/10.1016/j.coviro.2011.10.008] [PMID: 22328912]
[32]
Zhang N, Bao YJ, Tong AH, et al. Whole transcriptome analysis reveals differential gene expression profile reflecting macrophage polarization in response to influenza A H5N1 virus infection. BMC Med Genomics 2018; 11(1): 20.
[http://dx.doi.org/10.1186/s12920-018-0335-0] [PMID: 29475453]
[33]
Ye J, Chen S, Maniatis T. Cardiac glycosides are potent inhibitors of interferon-β gene expression. Nat Chem Biol 2011; 7(1): 25-33.
[http://dx.doi.org/10.1038/nchembio.476] [PMID: 21076398]
[34]
Luterek-Puszyńska K, Malinowski D, Paradowska-Gorycka A, Safranow K, Pawlik A. CD28, CTLA-4 and CCL5 gene polymorphisms in patients with rheumatoid arthritis. Clin Rheumatol 2017; 36(5): 1129-35.
[http://dx.doi.org/10.1007/s10067-016-3496-2] [PMID: 27988812]
[35]
Lee SH, Lee HS, Park G, Oh SM, Oh DS. Dual actions on gout flare and acute kidney injury along with enhanced renal transporter activities by Yokuininto, a Kampo medicine. BMC Complement Altern Med 2019; 19(1): 57.
[http://dx.doi.org/10.1186/s12906-019-2469-9] [PMID: 30871515]
[36]
Elenkov IJ, Iezzoni DG, Daly A, Harris AG, Chrousos GP. Cytokine dysregulation, inflammation and well-being. Neuroimmunomodulation 2005; 12(5): 255-69.
[http://dx.doi.org/10.1159/000087104] [PMID: 16166805]
[37]
Okamoto M, Toyama M, Baba M. The chemokine receptor antagonist cenicriviroc inhibits the replication of SARS-CoV-2 in vitro. Antiviral Res 2020; 182: 104902.
[http://dx.doi.org/10.1016/j.antiviral.2020.104902] [PMID: 32739404]
[38]
Cheng W, Jia H, Wang X, et al. Ectromelia virus upregulates the expression of heat shock protein 70 to promote viral replication. Int J Mol Med 2018; 42(2): 1044-53.
[PMID: 29749430]
[39]
Zhong C, Li J, Mao L, et al. Proteomics analysis reveals heat shock proteins involved in caprine parainfluenza virus type 3 infection. BMC Vet Res 2019; 15(1): 151.
[http://dx.doi.org/10.1186/s12917-019-1897-6] [PMID: 31101113]
[40]
Bonam SR, Ruff M, Muller S. HSPA8/HSC70 in Immune Disorders: A Molecular Rheostat that Adjusts Chaperone-Mediated Autophagy Substrates. Cells 2019; 8(8): E849.
[http://dx.doi.org/10.3390/cells8080849] [PMID: 31394830]
[41]
Zhu P, Lv C, Fang C, et al. Heat shock protein member 8 is an attachment factor for infectious bronchitis virus. Front Microbiol 2020; 11: 1630.
[http://dx.doi.org/10.3389/fmicb.2020.01630] [PMID: 32765462]
[42]
Jiang Y, Liu N, Zhu S, Hu X, Chang D, Liu J. Elucidation of the Mechanisms and Molecular Targets of Yiqi Shexue Formula for Treatment of Primary Immune Thrombocytopenia Based on Network Pharmacology. Front Pharmacol 2019; 10: 1136.
[http://dx.doi.org/10.3389/fphar.2019.01136] [PMID: 31632275]
[43]
Öhman T, Söderholm S, Paidikondala M, Lietzén N, Matikainen S, Nyman TA. Phosphoproteome characterization reveals that Sendai virus infection activates mTOR signaling in human epithelial cells. Proteomics 2015; 15(12): 2087-97.
[http://dx.doi.org/10.1002/pmic.201400586] [PMID: 25764225]
[44]
Ramaiah MJ. mTOR inhibition and p53 activation, microRNAs: The possible therapy against pandemic COVID-19. Gene Rep 2020; 20: 100765.
[http://dx.doi.org/10.1016/j.genrep.2020.100765] [PMID: 32835132]
[45]
Appelberg S, Gupta S, Svensson Akusjärvi S, et al. Dysregulation in Akt/mTOR/HIF-1 signaling identified by proteo-transcriptomics of SARS-CoV-2 infected cells. Emerg Microbes Infect 2020; 9(1): 1748-60.
[http://dx.doi.org/10.1080/22221751.2020.1799723] [PMID: 32691695]
[46]
Tang Y, Kwiatkowski DJ, Henske EP. mTORC1 Hyperactivation in LAM Leads to ACE2 Upregulation in Type II Pneumocytes: Implications for COVID-19. The European respiratory journal: Official journal of the European Society for Clinical Respiratory Physiology 2020.
[47]
Ziegler CGK, Allon SJ, Nyquist SK, et al. SARS-CoV-2 receptor ACE2 is an interferon-stimulated gene in human airway epithelial cells and is detected in specific cell subsets across tissues. Cell 2020; 181(5): 1016-1035.e19.
[http://dx.doi.org/10.1016/j.cell.2020.04.035] [PMID: 32413319]

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