Lactate facilitates classical swine fever virus replication by enhancing cholesterol biosynthesis

Xiaodong Zou; Yang Yang; Feng Lin; Jiahuan Chen; Huanyu Zhang; Linquan Li; Hongsheng Ouyang; Daxin Pang; Linzhu Ren; Xiaochun Tang

doi:10.1016/j.isci.2022.105353

Lactate facilitates classical swine fever virus replication by enhancing cholesterol biosynthesis

iScience. 2022 Oct 13;25(11):105353. doi: 10.1016/j.isci.2022.105353. eCollection 2022 Nov 18.

Authors

Xiaodong Zou¹, Yang Yang¹, Feng Lin¹, Jiahuan Chen¹, Huanyu Zhang¹, Linquan Li¹, Hongsheng Ouyang^{1

2}, Daxin Pang^{1

2}, Linzhu Ren¹, Xiaochun Tang^{1

2}

Affiliations

¹ College of Animal Sciences, Jilin University, Changchun, China.
² Chongqing Research Institute of Jilin University, Chongqing, China.

Abstract

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.

Keywords: Human metabolism; Virology.