Antiviral activity of Schizonepeta tenuifolia Briquet against noroviruses via induction of antiviral interferons

Ng, Yee Ching; Kim, Hyoun‐Ah; Lee, Jeong Su; Lee, Sung Joon; Song, Mee Hyun

doi:10.1007/s12275-018-8228-7

Cited by 18 publications

(12 citation statements)

References 39 publications

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“…MNV infection in RAW cells induces a strong innate immune response, including interferon induction (66). Type I interferons in turn are able to affect host cell metabolism (67, 68) and exhibit a strong anti-MNV response (69–71). Therefore, we determined whether 2DG inhibition of viral replication was dependent on type I interferon responses.…”

Section: Resultsmentioning

confidence: 99%

Glycolysis Is an Intrinsic Factor for Optimal Replication of a Norovirus

Passalacqua

Jia

Goodfellow

et al. 2019

mBio

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The metabolic pathways of central carbon metabolism, glycolysis and oxidative phosphorylation (OXPHOS), are important host factors that determine the outcome of viral infections and can be manipulated by some viruses to favor infection. However, mechanisms of metabolic modulation and their effects on viral replication vary widely. Herein, we present the first metabolomics and energetic profiling of norovirus-infected cells, which revealed increases in glycolysis, OXPHOS, and the pentose phosphate pathway (PPP) during murine norovirus (MNV) infection. Inhibiting glycolysis with 2-deoxyglucose (2DG) in macrophages revealed that glycolysis is an important factor for optimal MNV infection, while inhibiting the PPP and OXPHOS showed a relatively minor impact of these pathways on MNV infection. 2DG affected an early stage in the viral life cycle after viral uptake and capsid uncoating, leading to decreased viral protein production and viral RNA. The requirement of glycolysis was specific for MNV (but not astrovirus) infection, independent of the type I interferon antiviral response, and unlikely to be due to a lack of host cell nucleotide synthesis. MNV infection increased activation of the protein kinase Akt, but not AMP-activated protein kinase (AMPK), two master regulators of cellular metabolism, implicating Akt signaling in upregulating host metabolism during norovirus infection. In conclusion, our findings suggest that the metabolic state of target cells is an intrinsic host factor that determines the extent of norovirus replication and implicates glycolysis as a virulence determinant. They further point to cellular metabolism as a novel therapeutic target for norovirus infections and improvements in current human norovirus culture systems. IMPORTANCE Viruses depend on the host cells they infect to provide the machinery and substrates for replication. Host cells are highly dynamic systems that can alter their intracellular environment and metabolic behavior, which may be helpful or inhibitory for an infecting virus. In this study, we show that macrophages, a target cell of murine norovirus (MNV), increase glycolysis upon viral infection, which is important for early steps in MNV infection. Human noroviruses (hNoV) are a major cause of gastroenteritis globally, causing enormous morbidity and economic burden. Currently, no effective antivirals or vaccines exist for hNoV, mainly due to the lack of high-efficiency in vitro culture models for their study. Thus, insights gained from the MNV model may reveal aspects of host cell metabolism that can be targeted for improving hNoV cell culture systems and for developing effective antiviral therapies.

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Section: Resultsmentioning

confidence: 99%

Glycolysis Is an Intrinsic Factor for Optimal Replication of a Norovirus

Passalacqua

Jia

Goodfellow

et al. 2019

mBio

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“…[6] Chemical studies revealed that SS contained volatile oils, flavonoids, organic acids, etc. [7][8][9] Research into pharmacological activities of the oils accumulated by SS possesses anti-inflammatory, [10] antioxidant, [11] analgesia, [12] antineoplastic [13,14] and antiviral [15,16] properties. Thus, the volatile components could be selected as marker compounds for quality evaluation of SS.…”

Section: Introductionmentioning

confidence: 99%

Color discrimination and gas chromatography-mass spectrometry fingerprint based on chemometrics analysis for the quality evaluation of Schizonepetae Spica

Liu

Zhang

et al. 2020

PLoS ONE

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Schizonepetae Spica (SS), the dried spike of Schizonepeta tenuifolia Briq., is a traditional Chinese medicinal herb. According to the color of persistent calyx, SS is categorized into two classes: the yellowish-green-type and the brownish-type. Based on the chemometrics analysis of gas chromatography-mass spectrometry (GC-MS), a novel model of identifying and evaluating the quality of SS in different colors was constructed for the first time in this work. 20 batches SS samples of different colors were collected and used to extract essential oils. The average essential oils yield of SS in yellowish-green color was significantly higher than that of SS in brownish color from the same origin (p<0.05). The GC-MS fingerprints of 20 batches SS samples whose correlation coefficients were over 0.964 demonstrated SS samples were consistent to some extent in spite of slightly different chemical indexes. A total of 39 common volatiles compounds were identified. Hierarchical clustering analysis (HCA), principal component analysis (PCA) and partial least-squares discriminate analysis (PLS-DA) were developed to distinguish SS samples characterized by different colors. Consistent results were obtained to show that SS samples could be successfully grouped according to their color. Finally, 4,5,6,7-tetrahydro-3,6-dimethyl-benzofuran and pulegone were detected as the key variables for discriminating SS samples of different colors and for quality control. The obtained results proved that SS of good quality were often yellowishgreen and those of poor quality were often brownish.

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“…MNV infection in RAW cells induces a strong innate immune response, including interferon induction (66). Type I Interferons in turn are able to affect host cell metabolism (67, 68), and exhibit a strong anti-MNV response (69–71). Therefore, we determined whether 2DG inhibition of viral replication was dependent on type I interferon responses.…”

Section: Resultsmentioning

confidence: 99%

Central carbon metabolism is an intrinsic factor for optimal replication of a norovirus

Jia

Goodfellow

et al. 2018

Preprint

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word count: 227 13 Manuscript word count: 4830 14 15 16 ABSTRACT 17The metabolic pathways of central carbon metabolism, glycolysis and oxidative phosphorylation 18 (OXPHOS), are important host factors that determine the outcome of viral infections and can 19 therefore be manipulated by some viruses to favor infection. However, mechanisms of metabolic 20 modulation and their effects on viral replication vary widely. Herein, we present the first 21 metabolomics profile of norovirus-infected cells, which revealed increases in glycolysis, 22 IMPORTANCE 38Viruses depend on the host cells they infect to provide the machinery and substrates for 39 replication. Host cells are highly dynamic systems that can alter their intracellular environment 40 and metabolic behavior, which may be helpful or inhibitory for an infecting virus. In this study, 41 we show that macrophages, a target cell of murine norovirus (MNV), increase central carbon 42 metabolism upon viral infection, which is important for early steps in MNV infection. Human 43 noroviruses (hNoV) are a major cause of gastroenteritis globally, causing enormous morbidity 44 and economic burden. Currently, no effective antivirals or vaccines exist for hNoV, mainly due 45 to the lack of high efficiency in vitro culture models for their study. Thus, insights gained from 46 the MNV model may reveal aspects of host cell metabolism that can be targeted for improving 47 hNoV cell culture systems and for developing effective antiviral therapies. 48 49

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Antiviral activity of Schizonepeta tenuifolia Briquet against noroviruses via induction of antiviral interferons

Cited by 18 publications

References 39 publications

Glycolysis Is an Intrinsic Factor for Optimal Replication of a Norovirus

Glycolysis Is an Intrinsic Factor for Optimal Replication of a Norovirus

Color discrimination and gas chromatography-mass spectrometry fingerprint based on chemometrics analysis for the quality evaluation of Schizonepetae Spica

Central carbon metabolism is an intrinsic factor for optimal replication of a norovirus

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