Metabolomics Exploration of Pseudorabies Virus Reprogramming Metabolic Profiles of PK-15 Cells to Enhance Viral Replication
For viral replication to occur in host cells, low-molecular-weight metabolites are necessary for virion assembly. Recently, metabolomics has shown great promise in uncovering the highly complex mechanisms associated with virus-host interactions. In this study, the metabolic networks in PK-15 cells i...
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Frontiers Media S.A.
2021-01-01
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Online Access: | https://www.frontiersin.org/articles/10.3389/fcimb.2020.599087/full |
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Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Hongchao Gou Hongchao Gou Hongchao Gou Hongchao Gou Zhibiao Bian Zhibiao Bian Zhibiao Bian Zhibiao Bian Yan Li Yan Li Yan Li Yan Li Rujian Cai Rujian Cai Rujian Cai Rujian Cai Zhiyong Jiang Zhiyong Jiang Zhiyong Jiang Zhiyong Jiang Shuai Song Shuai Song Shuai Song Shuai Song Kunli Zhang Kunli Zhang Kunli Zhang Kunli Zhang Pinpin Chu Pinpin Chu Pinpin Chu Pinpin Chu Dongxia Yang Dongxia Yang Dongxia Yang Dongxia Yang Chunling Li Chunling Li Chunling Li Chunling Li |
spellingShingle |
Hongchao Gou Hongchao Gou Hongchao Gou Hongchao Gou Zhibiao Bian Zhibiao Bian Zhibiao Bian Zhibiao Bian Yan Li Yan Li Yan Li Yan Li Rujian Cai Rujian Cai Rujian Cai Rujian Cai Zhiyong Jiang Zhiyong Jiang Zhiyong Jiang Zhiyong Jiang Shuai Song Shuai Song Shuai Song Shuai Song Kunli Zhang Kunli Zhang Kunli Zhang Kunli Zhang Pinpin Chu Pinpin Chu Pinpin Chu Pinpin Chu Dongxia Yang Dongxia Yang Dongxia Yang Dongxia Yang Chunling Li Chunling Li Chunling Li Chunling Li Metabolomics Exploration of Pseudorabies Virus Reprogramming Metabolic Profiles of PK-15 Cells to Enhance Viral Replication Frontiers in Cellular and Infection Microbiology metabolomics metabolic activity pseudorabies virus (PRV) variant virulent strain classical attenuated strain PK-15 cells |
author_facet |
Hongchao Gou Hongchao Gou Hongchao Gou Hongchao Gou Zhibiao Bian Zhibiao Bian Zhibiao Bian Zhibiao Bian Yan Li Yan Li Yan Li Yan Li Rujian Cai Rujian Cai Rujian Cai Rujian Cai Zhiyong Jiang Zhiyong Jiang Zhiyong Jiang Zhiyong Jiang Shuai Song Shuai Song Shuai Song Shuai Song Kunli Zhang Kunli Zhang Kunli Zhang Kunli Zhang Pinpin Chu Pinpin Chu Pinpin Chu Pinpin Chu Dongxia Yang Dongxia Yang Dongxia Yang Dongxia Yang Chunling Li Chunling Li Chunling Li Chunling Li |
author_sort |
Hongchao Gou |
title |
Metabolomics Exploration of Pseudorabies Virus Reprogramming Metabolic Profiles of PK-15 Cells to Enhance Viral Replication |
title_short |
Metabolomics Exploration of Pseudorabies Virus Reprogramming Metabolic Profiles of PK-15 Cells to Enhance Viral Replication |
title_full |
Metabolomics Exploration of Pseudorabies Virus Reprogramming Metabolic Profiles of PK-15 Cells to Enhance Viral Replication |
title_fullStr |
Metabolomics Exploration of Pseudorabies Virus Reprogramming Metabolic Profiles of PK-15 Cells to Enhance Viral Replication |
title_full_unstemmed |
Metabolomics Exploration of Pseudorabies Virus Reprogramming Metabolic Profiles of PK-15 Cells to Enhance Viral Replication |
title_sort |
metabolomics exploration of pseudorabies virus reprogramming metabolic profiles of pk-15 cells to enhance viral replication |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Cellular and Infection Microbiology |
issn |
2235-2988 |
publishDate |
2021-01-01 |
description |
For viral replication to occur in host cells, low-molecular-weight metabolites are necessary for virion assembly. Recently, metabolomics has shown great promise in uncovering the highly complex mechanisms associated with virus-host interactions. In this study, the metabolic networks in PK-15 cells infected with a variant virulent or classical attenuated pseudorabies virus (PRV) strains were explored using gas chromatography-mass spectrometry (GC-MS) analysis. Although total numbers of metabolites whose levels were altered by infection with the variant virulent strain or the classical attenuated strain were different at 8 and 16 h post infection (hpi), the predicted levels of differential metabolic components were shown to be associated with specific pathways, including glycolysis as well as amino acid and nucleotide metabolism. The glucose depletion and glycolysis inhibitors 2DG and oxamate could reduce the level of PRV replication in PK-15 cells. In addition, the inhibition of the pentose phosphate pathway (PPP) resulted in an obvious decline of viral titers, but the prevention of oxidative phosphorylation in the tricarboxylic acid (TCA) cycle had a minimal effect on viral replication. Glutamine starvation resulted in the decline of viral titers, which could be restored by supplemental addition in the culture media. However, inhibition of glutaminase (GLS) activity or the supplement of 2-ketoglutarate into glutamine-deleted DMEM did not alter PRV replication in PK-15 cells. The results of the current study indicate that PRV reprograms the metabolic activities of PK-15 cells. The metabolic flux from glycolysis, PPP and glutamine metabolism to nucleotide biosynthesis was essential for PRV to enhance its replication. This study will help to identify the biochemical materials utilized by PRV replication in host cells, and this knowledge can aid in developing new antiviral strategies. |
topic |
metabolomics metabolic activity pseudorabies virus (PRV) variant virulent strain classical attenuated strain PK-15 cells |
url |
https://www.frontiersin.org/articles/10.3389/fcimb.2020.599087/full |
work_keys_str_mv |
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doaj-36c6563ce9ad4225966b8aa2ca6bc3552021-01-29T13:45:19ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882021-01-011010.3389/fcimb.2020.599087599087Metabolomics Exploration of Pseudorabies Virus Reprogramming Metabolic Profiles of PK-15 Cells to Enhance Viral ReplicationHongchao Gou0Hongchao Gou1Hongchao Gou2Hongchao Gou3Zhibiao Bian4Zhibiao Bian5Zhibiao Bian6Zhibiao Bian7Yan Li8Yan Li9Yan Li10Yan Li11Rujian Cai12Rujian Cai13Rujian Cai14Rujian Cai15Zhiyong Jiang16Zhiyong Jiang17Zhiyong Jiang18Zhiyong Jiang19Shuai Song20Shuai Song21Shuai Song22Shuai Song23Kunli Zhang24Kunli Zhang25Kunli Zhang26Kunli Zhang27Pinpin Chu28Pinpin Chu29Pinpin Chu30Pinpin Chu31Dongxia Yang32Dongxia Yang33Dongxia Yang34Dongxia Yang35Chunling Li36Chunling Li37Chunling Li38Chunling Li39Institute of Animal Health, Guangdong Academy of Agricultural Sciences, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Livestock Disease Prevention, Guangzhou, ChinaGuangdong Open Laboratory of Veterinary Public Health, Guangzhou, ChinaScientific Observation and Experiment Station of Veterinary Drugs and Diagnostic Techniques of Guangdong Province, Guangzhou, ChinaInstitute of Animal Health, Guangdong Academy of Agricultural Sciences, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Livestock Disease Prevention, Guangzhou, ChinaGuangdong Open Laboratory of Veterinary Public Health, Guangzhou, ChinaScientific Observation and Experiment Station of Veterinary Drugs and Diagnostic Techniques of Guangdong Province, Guangzhou, ChinaInstitute of Animal Health, Guangdong Academy of Agricultural Sciences, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Livestock Disease Prevention, Guangzhou, ChinaGuangdong Open Laboratory of Veterinary Public Health, Guangzhou, ChinaScientific Observation and Experiment Station of Veterinary Drugs and Diagnostic Techniques of Guangdong Province, Guangzhou, ChinaInstitute of Animal Health, Guangdong Academy of Agricultural Sciences, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Livestock Disease Prevention, Guangzhou, ChinaGuangdong Open Laboratory of Veterinary Public Health, Guangzhou, ChinaScientific Observation and Experiment Station of Veterinary Drugs and Diagnostic Techniques of Guangdong Province, Guangzhou, ChinaInstitute of Animal Health, Guangdong Academy of Agricultural Sciences, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Livestock Disease Prevention, Guangzhou, ChinaGuangdong Open Laboratory of Veterinary Public Health, Guangzhou, ChinaScientific Observation and Experiment Station of Veterinary Drugs and Diagnostic Techniques of Guangdong Province, Guangzhou, ChinaInstitute of Animal Health, Guangdong Academy of Agricultural Sciences, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Livestock Disease Prevention, Guangzhou, ChinaGuangdong Open Laboratory of Veterinary Public Health, Guangzhou, ChinaScientific Observation and Experiment Station of Veterinary Drugs and Diagnostic Techniques of Guangdong Province, Guangzhou, ChinaInstitute of Animal Health, Guangdong Academy of Agricultural Sciences, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Livestock Disease Prevention, Guangzhou, ChinaGuangdong Open Laboratory of Veterinary Public Health, Guangzhou, ChinaScientific Observation and Experiment Station of Veterinary Drugs and Diagnostic Techniques of Guangdong Province, Guangzhou, ChinaInstitute of Animal Health, Guangdong Academy of Agricultural Sciences, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Livestock Disease Prevention, Guangzhou, ChinaGuangdong Open Laboratory of Veterinary Public Health, Guangzhou, ChinaScientific Observation and Experiment Station of Veterinary Drugs and Diagnostic Techniques of Guangdong Province, Guangzhou, ChinaInstitute of Animal Health, Guangdong Academy of Agricultural Sciences, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Livestock Disease Prevention, Guangzhou, ChinaGuangdong Open Laboratory of Veterinary Public Health, Guangzhou, ChinaScientific Observation and Experiment Station of Veterinary Drugs and Diagnostic Techniques of Guangdong Province, Guangzhou, ChinaInstitute of Animal Health, Guangdong Academy of Agricultural Sciences, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Livestock Disease Prevention, Guangzhou, ChinaGuangdong Open Laboratory of Veterinary Public Health, Guangzhou, ChinaScientific Observation and Experiment Station of Veterinary Drugs and Diagnostic Techniques of Guangdong Province, Guangzhou, ChinaFor viral replication to occur in host cells, low-molecular-weight metabolites are necessary for virion assembly. Recently, metabolomics has shown great promise in uncovering the highly complex mechanisms associated with virus-host interactions. In this study, the metabolic networks in PK-15 cells infected with a variant virulent or classical attenuated pseudorabies virus (PRV) strains were explored using gas chromatography-mass spectrometry (GC-MS) analysis. Although total numbers of metabolites whose levels were altered by infection with the variant virulent strain or the classical attenuated strain were different at 8 and 16 h post infection (hpi), the predicted levels of differential metabolic components were shown to be associated with specific pathways, including glycolysis as well as amino acid and nucleotide metabolism. The glucose depletion and glycolysis inhibitors 2DG and oxamate could reduce the level of PRV replication in PK-15 cells. In addition, the inhibition of the pentose phosphate pathway (PPP) resulted in an obvious decline of viral titers, but the prevention of oxidative phosphorylation in the tricarboxylic acid (TCA) cycle had a minimal effect on viral replication. Glutamine starvation resulted in the decline of viral titers, which could be restored by supplemental addition in the culture media. However, inhibition of glutaminase (GLS) activity or the supplement of 2-ketoglutarate into glutamine-deleted DMEM did not alter PRV replication in PK-15 cells. The results of the current study indicate that PRV reprograms the metabolic activities of PK-15 cells. The metabolic flux from glycolysis, PPP and glutamine metabolism to nucleotide biosynthesis was essential for PRV to enhance its replication. This study will help to identify the biochemical materials utilized by PRV replication in host cells, and this knowledge can aid in developing new antiviral strategies.https://www.frontiersin.org/articles/10.3389/fcimb.2020.599087/fullmetabolomicsmetabolic activitypseudorabies virus (PRV)variant virulent strainclassical attenuated strainPK-15 cells |