Zou Xiaodong, Yang Yang, Lin Feng, Chen Jiahuan, Zhang Huanyu, Li Linquan, Ouyang Hongsheng, Pang Daxin, Ren Linzhu, Tang Xiaochun
College of Animal Sciences, Jilin University, Changchun, China.
Chongqing Research Institute of Jilin University, Chongqing, China.
iScience. 2022 Oct 13;25(11):105353. doi: 10.1016/j.isci.2022.105353. eCollection 2022 Nov 18.
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.
病毒学中一个新兴的话题是病毒复制与宿主细胞的代谢重编程密切相关。了解经典猪瘟病毒（CSFV）感染导致的宿主细胞代谢重编程的影响及其潜在机制将有助于控制经典猪瘟（CSF）的传播。在本研究中，我们发现CSFV感染增强了PK-15细胞中的有氧糖酵解。用2-脱氧-D-葡萄糖阻断糖酵解或破坏酶PFKL和LDHA可降低CSFV复制。乳酸被确定为CSFV复制中的一个重要分子，与磷酸戊糖途径和三羧酸循环无关。进一步分析表明，细胞中积累的乳酸促进了胆固醇生物合成，这有助于CSFV复制并在CSFV复制过程中破坏I型干扰素反应，而胆固醇合成的破坏消除了乳酸对CSFV复制的影响。这些结果为CSFV复杂的病理机制提供了更多见解。
