Lactate facilitates classical swine fever virus replication by enhancing cholesterol biosynthesis

Summary: An emerging topic in virology is that viral replication is closely linked with the metabolic reprogramming of host cells. Understanding the effects of reprogramming host cell metabolism due to classical swine fever virus (CSFV) infection and the underling mechanisms would facilitate control...

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Main Authors: Xiaodong Zou, Yang Yang, Feng Lin, Jiahuan Chen, Huanyu Zhang, Linquan Li, Hongsheng Ouyang, Daxin Pang, Linzhu Ren, Xiaochun Tang
Format: Article
Language:English
Published: Elsevier 2022-11-01
Series:iScience
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S258900422201625X
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author Xiaodong Zou
Yang Yang
Feng Lin
Jiahuan Chen
Huanyu Zhang
Linquan Li
Hongsheng Ouyang
Daxin Pang
Linzhu Ren
Xiaochun Tang
author_facet Xiaodong Zou
Yang Yang
Feng Lin
Jiahuan Chen
Huanyu Zhang
Linquan Li
Hongsheng Ouyang
Daxin Pang
Linzhu Ren
Xiaochun Tang
author_sort Xiaodong Zou
collection DOAJ
description Summary: An emerging topic in virology is that viral replication is closely linked with the metabolic reprogramming of host cells. Understanding the effects of reprogramming host cell metabolism due to classical swine fever virus (CSFV) infection and the underling mechanisms would facilitate controlling the spread of classical swine fever (CSF). In the current study, we found that CSFV infection enhanced aerobic glycolysis in PK-15 cells. Blocking glycolysis with 2-deoxy-d-glycose or disrupting the enzymes PFKL and LDHA decreased CSFV replication. Lactate was identified as an important molecule in CSFV replication, independent of the pentose phosphate pathway and tricarboxylic acid cycle. Further analysis demonstrated that the accumulated lactate in cells promoted cholesterol biosynthesis, which facilitated CSFV replication and disrupted the type I interferon response during CSFV replication, and the disruption of cholesterol synthesis abolished the lactate effects on CSFV replication. The results provided more insights into the complex pathological mechanisms of CSFV.
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spelling doaj.art-f2fa7d40c14f445b9a945721e59532ad2022-12-22T03:27:33ZengElsevieriScience2589-00422022-11-012511105353Lactate facilitates classical swine fever virus replication by enhancing cholesterol biosynthesisXiaodong Zou0Yang Yang1Feng Lin2Jiahuan Chen3Huanyu Zhang4Linquan Li5Hongsheng Ouyang6Daxin Pang7Linzhu Ren8Xiaochun Tang9College of Animal Sciences, Jilin University, Changchun, ChinaCollege of Animal Sciences, Jilin University, Changchun, ChinaCollege of Animal Sciences, Jilin University, Changchun, ChinaCollege of Animal Sciences, Jilin University, Changchun, ChinaCollege of Animal Sciences, Jilin University, Changchun, ChinaCollege of Animal Sciences, Jilin University, Changchun, ChinaCollege of Animal Sciences, Jilin University, Changchun, China; Chongqing Research Institute of Jilin University, Chongqing, ChinaCollege of Animal Sciences, Jilin University, Changchun, China; Chongqing Research Institute of Jilin University, Chongqing, ChinaCollege of Animal Sciences, Jilin University, Changchun, China; Corresponding authorCollege of Animal Sciences, Jilin University, Changchun, China; Chongqing Research Institute of Jilin University, Chongqing, China; Corresponding authorSummary: An emerging topic in virology is that viral replication is closely linked with the metabolic reprogramming of host cells. Understanding the effects of reprogramming host cell metabolism due to classical swine fever virus (CSFV) infection and the underling mechanisms would facilitate controlling the spread of classical swine fever (CSF). In the current study, we found that CSFV infection enhanced aerobic glycolysis in PK-15 cells. Blocking glycolysis with 2-deoxy-d-glycose or disrupting the enzymes PFKL and LDHA decreased CSFV replication. Lactate was identified as an important molecule in CSFV replication, independent of the pentose phosphate pathway and tricarboxylic acid cycle. Further analysis demonstrated that the accumulated lactate in cells promoted cholesterol biosynthesis, which facilitated CSFV replication and disrupted the type I interferon response during CSFV replication, and the disruption of cholesterol synthesis abolished the lactate effects on CSFV replication. The results provided more insights into the complex pathological mechanisms of CSFV.http://www.sciencedirect.com/science/article/pii/S258900422201625XVirologyHuman metabolism
spellingShingle Xiaodong Zou
Yang Yang
Feng Lin
Jiahuan Chen
Huanyu Zhang
Linquan Li
Hongsheng Ouyang
Daxin Pang
Linzhu Ren
Xiaochun Tang
Lactate facilitates classical swine fever virus replication by enhancing cholesterol biosynthesis
iScience
Virology
Human metabolism
title Lactate facilitates classical swine fever virus replication by enhancing cholesterol biosynthesis
title_full Lactate facilitates classical swine fever virus replication by enhancing cholesterol biosynthesis
title_fullStr Lactate facilitates classical swine fever virus replication by enhancing cholesterol biosynthesis
title_full_unstemmed Lactate facilitates classical swine fever virus replication by enhancing cholesterol biosynthesis
title_short Lactate facilitates classical swine fever virus replication by enhancing cholesterol biosynthesis
title_sort lactate facilitates classical swine fever virus replication by enhancing cholesterol biosynthesis
topic Virology
Human metabolism
url http://www.sciencedirect.com/science/article/pii/S258900422201625X
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AT jiahuanchen lactatefacilitatesclassicalswinefevervirusreplicationbyenhancingcholesterolbiosynthesis
AT huanyuzhang lactatefacilitatesclassicalswinefevervirusreplicationbyenhancingcholesterolbiosynthesis
AT linquanli lactatefacilitatesclassicalswinefevervirusreplicationbyenhancingcholesterolbiosynthesis
AT hongshengouyang lactatefacilitatesclassicalswinefevervirusreplicationbyenhancingcholesterolbiosynthesis
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AT linzhuren lactatefacilitatesclassicalswinefevervirusreplicationbyenhancingcholesterolbiosynthesis
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