Elucidation of the Inhibitory Mechanisms of Nipponoparmelia laevior Lichen Extract against Influenza A (H1N1) Virus through Proteomic Analyses
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Lichens contain diverse bioactive secondary metabolites with various chemical and biological properties, which have been widely studied. However, details of the inhibitory mechanisms of their secondary metabolites against influenza A virus (IAV) have not been documented. Here, we investigated the antiviral effect of lichen extracts, obtained from South Korea, against IAV in MDCK cells. Of the lichens tested, Nipponoparmelia laevior (LC24) exhibited the most potent inhibitory effect against IAV infection. LC24 extract significantly increased cell viability, and reduced apoptosis in IAV-infected cells. The LC24 extract also markedly reduced (~ 3.2 logfold) IAV mRNA expression after 48 h of infection. To understand the antiviral mechanism of LC24 against IAV, proteomic (UPLC-HDMSE) analysis was performed to compare proteome modulation in IAV-infected (V) vs. mock (M) and LC24+IAV (LCV) vs. V cells. Based on Ingenuity Pathway Analysis (IPA), LC24 inhibited IAV infection by modulating several antiviral-related genes and proteins (HSPA4, HSPA5, HSPA8, ANXA1, ANXA2, HIF-1α, AKT1, MX1, HNRNPH1, HNRNPDL, PDIA3, and VCP) via different signaling pathways, including HIF-1α signaling, unfolded protein response, and interferon signaling. These molecules were identified as the specific biomarkers for controlling IAV in vitro and further confirmation of their potential against IAV in vivo is required. Our findings provide a platform for further studies on the application of lichen extracts against IAV.
Abstract
Lichens contain diverse bioactive secondary metabolites with various chemical and biological properties, which have been widely studied. However, details of the inhibitory mechanisms of their secondary metabolites against influenza A virus (IAV) have not been documented. Here, we investigated the antiviral effect of lichen extracts, obtained from South Korea, against IAV in MDCK cells. Of the lichens tested, Nipponoparmelia laevior (LC24) exhibited the most potent inhibitory effect against IAV infection. LC24 extract significantly increased cell viability, and reduced apoptosis in IAV-infected cells. The LC24 extract also markedly reduced (~ 3.2 logfold) IAV mRNA expression after 48 h of infection. To understand the antiviral mechanism of LC24 against IAV, proteomic (UPLC-HDMSE) analysis was performed to compare proteome modulation in IAV-infected (V) vs. mock (M) and LC24+IAV (LCV) vs. V cells. Based on Ingenuity Pathway Analysis (IPA), LC24 inhibited IAV infection by modulating several antiviral-related genes and proteins (HSPA4, HSPA5, HSPA8, ANXA1, ANXA2, HIF-1α, AKT1, MX1, HNRNPH1, HNRNPDL, PDIA3, and VCP) via different signaling pathways, including HIF-1α signaling, unfolded protein response, and interferon signaling. These molecules were identified as the specific biomarkers for controlling IAV in vitro and further confirmation of their potential against IAV in vivo is required. Our findings provide a platform for further studies on the application of lichen extracts against IAV.
참고문헌 (49)
- Long JS, "Host and viral determinants of influenza A virus species specificity", Nat. Rev. Microbiol, 17, pp.67~81 (2019)
- Dou D, "Influenza A virus cell entry, replication, virion assembly and movement", Front Immunol, 9, pp.1581~ (2018)
- Medina RA, "1918 Influenza Virus: 100 years on, are we prepared against the next influenza pandemic?", Nat, Rev. Microbiol, 16, pp.61~62 (2018)
- WHO, "Influenza (seasonal)", Influenza, ~ (2019)
- Ju H, "Inhibitors of influenza virus polymerase acidic(PA)endonuclease : contemporary developments and perspectives", J. Med. Chem, 60, pp.3533~3551 (2017)
- van de Wakker SI, "New drug-strategies to tackle viral-host interactions for the treatment of influenza virus infections", Eur. J. Pharmacol, 809, pp.178~190 (2017)
- Regoes RR, "Emergence of drug-resistant influenza virus : population dynamical considerations", Science, 312, pp.389~391 (2006)
- Kaasalainen U, "Cyanobacteria produce a high variety of hepatotoxic peptides in lichen symbiosis", Proc. Natl. Acad. Sci. USA, 109, pp.5886~5891 (2012)
- Shukla V, "Lichens as a potential natural source of bioactive compounds : a review", Phytochem. Rev, 9, pp.303~314 (2010)
- Feuerer T, "Biodiversity of lichens, including a world-wide analysis of checklist data based on Takhtajan’s floristic regions", Biodivers. Conserv, 16, pp.85~98 (2007)
- Ahmadjian V, "Lichens are more important than you think", Bioscience, 45, pp.124~ (1995)
- Stocker-Wörgötter E, "Metabolic diversity of lichenforming ascomycetous fungi : culturing, polyketide and shikimatemetabolite production, and PKS genes", Nat. Prod. Rep, 25, pp.188~200 (2008)
- Zhou R, "The lichen secondary metabolite atranorin suppresses lung cancer cell motility and tumorigenesis", Sci. Rep, 7, pp.8136~ (2017)
- Nguyen TT, "Lichen secondary metabolites in Flavocetraria cucullata exhibit anti-cancer effects on human cancer cells through the induction of apoptosis and suppression of tumorigenic potentials", PLoS One, 9, pp.e111575~ (2014)
- Yilmaz M, "The antimicrobial activity of extracts of the lichen Cladonia foliacea and its(-)-usnic acid, atranorin, and fumarprotocetraric acid constituents", Z. Naturforsch C, 59(3-4), pp.249~254 (2004)
- Honda NK, "Parmotrema screminiae (Parmeliaceae), a novel lichen species from Brazil with potent antimicrobial activity", Orbital - Electron J. Chem, 8, pp.334~340 (2016)
- Kosanić M, "Antioxidant properties of some lichen species", J. Food Sci. Technol, 48, pp.584~590 (2011)
- Brisdelli F, "Cytotoxic activity and antioxidant capacity of purified lichen metabolites : an in vitro study", Phyther. Res, 27, pp.431~437 (2013)
- Perry NB, "Antimicrobial, antiviral and cytotoxic activity of New Zealand lichens", Lichenologist, 31, pp.627~636 (1999)
- Daowan Lai, "Phenolic compounds with in vitro activity against respiratory syncytial virus from the Nigerian lichen Ramalina farinacea", Planta Med, 79, pp.1440~1446 (2013)
- Esimone CO, "In vitro evaluation of the antiviral activity of extracts from the lichen Parmelia perlata (L,) Ach. against three RNA viruses", J. Infect. Dev. Ctries, 1, pp.315~320 (2007)
- Vu TH, "Depsides : Lichen metabolites active against hepatitis C virus", PLoS One, 10(3), pp.e120405~ (2015)
- Tanas S, "Evaluation of anti-inflammatory and antioxidan activities of Peltigera rufescens lichen species in acute and chronic inflammation models", J. Nat. Med, 64, pp.42~49 (2010)
- Studzińska-Sroka E, "Lichens as a source of chemical compounds with anti-inflammatory activity", Herba Polanica, 64, pp.56~64 (2018)
- Sokolov DN, "Anti-viral activity of(-)-and(+)-usnic acids and their derivatives against influenza virus A(H1N1)2009", Bioorg. Med. Chem. Lett, 22, pp.7060~7064 (2012)
- Shtro AA, "Novel derivatives of usnic acid effectively inhibiting reproduction of influenza A virus", Bioorg. Med. Chem, 22, pp.6826~6836 (2014)
- Shtro A, "Derivatives of usnic acid inhibit broad range of influenza viruses and protect mice from lethal influenza infection", Antivir. Chem. Chemother, 24, pp.92~98 (2015)
- Vaidya B, "Effectiveness of periodic treatment of quercetin against influenza A virus H1N1 through modulation of protein expression", J. Agric. Food Chem, 64, pp.4416~4425 (2016)
- Lu X, "Tube-Gel Digestion", Mol. Cell Proteomics, 4, pp.1948~1958 (2005)
- Yang H-Y, "Proteomic analysis of protein expression affected by peroxiredoxin V knock-down in hypoxic kidney", J. Proteome Res, 9, pp.4003~4015 (2010)
- Burniston JG, "Label-free profiling of skeletal muscle using highdefinition mass spectrometry", Proteomics, 14, pp.2339~2344 (2014)
- Saeed AI, "TM4 : A free, open-source system for microarray data management and analysis", Biotechniques, 34, pp.374~378 (2003)
- Muramoto Y, "Identification of novel influenza A virus proteins translated from PA mRNA", J. Virol, 87, pp.2455~2462 (2013)
- Fernández-Moriano C, "In vitro neuroprotective potential of lichen metabolite fumarprotocetraric acid via intracellular redox modulation", Toxicol. Appl. Pharmacol, 316, pp.83~94 (2017)
- Fernández-Moriano C, "Protective effects of lichen metabolites evernic and usnic acids against redox impairment-mediated cytotoxicity in central nervous system-like cells", Food Chem. Toxicol, 105, pp.262~277 (2017)
- Denisova O V, "Akt inhibitor MK2206 prevents influenza pH1N1 virus infection in vitro", Antimicrob. Agents Chemother, 58, pp.3689~3696 (2014)
- Guo X, "Nuclear translocation of HIF-1α induced by influenza A(H1N1)infection is critical to the production of proinflammatory cytokines", Emerg. Microbes Infect, 6(5), pp.e39~ (2017)
- Cha IS, "Heat shock protein profiles on the protein and gene expression levels in olive flounder kidney infected with Streptococcus parauberis", Fish Shellfish Immunol, 34, pp.1455~1462 (2013)
- Kajihara M, "Heat shock protein 70 modulates influenza A virus polymerase activity", J. Biol. Chem, 289, pp.7599~7614 (2014)
- Batra J, "Human heat shock protein 40(Hsp40", DnaJB1)promotes influenza A virus replication by assisting nuclear import of viral ribonucleoproteins, 2016, pp.6, 19063~
- Mirsaeidi M, "Annexins family : insights into their functions and potential role in pathogenesis of sarcoidosis", J. Transl. Med, 14, pp.89~97 (2016)
- Arora S, "Influenza A virus enhances its propagation through the modulation of Annexin-A1 dependent endosomal trafficking and apoptosis", Cell Death Differ, 23, pp.1243~1256 (2016)
- Ma Y, "Annexin A2(ANXA2)interacts with nonstructural protein 1 and promotes the replication of highly pathogenic H5N1 avian influenza virus", BMC Microbiol, 17, pp.191~199 (2017)
- LeBouder F, "Plasminogen promotes influenza A virus replication through an annexin 2-dependent pathway in the absence of neuraminidase", J. Gen. Virol, 91, pp.2753~2761 (2010)
- Chang C-W, "Mechanism of action of the suppression of influenza virus replication by Ko-Ken Tang through inhibition of the phosphatidylinositol 3-kinase", Akt signaling pathway and viral RNP nuclear export, 2011, pp.134, 614~623
- Werth N, "Activation of hypoxia inducible factor 1 is a general phenomenon in infections with human pathogens", PLoS One, 5, pp.e11576~ (2010)
- Ren L, "Influenza A virus(H1N1)triggers a hypoxic response by stabilizing hypoxia-inducible factor-1α via inhibition of proteasome", Virology, 530, pp.51~58 (2019)
- Shrestha N, "Eukaryotic initiation factor 2(eIF2)signaling regulates proinflammatory cytokine expression and bacterial invasion", J. Biol. Chem, 287, pp.28738~28744 (2012)
- Verhelst J, "Interferon-inducible protein MX1 inhibits influenza virus by interfering with functional viral ribonucleoprotein complex assembly", J. Virol, 86, pp.13445~13455 (2012)
