title: HMG-CoA reductase is negatively associated with PCV2 infection and PCV2-induced apoptotic cell death.
abstract: We examined the role of HMG-CoA reductase (HMGCR) during porcine circovirus 2 (PCV2) infection. The results demonstrated that levels of endogenous HMGCR were not significantly different in PCV2-infected cells and mock-infected cells. However, the level of phosphorylated HMGCR, an inactivated form of HMGCR, was increased in PCV2-infected cells. Furthermore, HMGCR was upregulated by overexpression, silenced by siRNA or inactivated using its dominant-negative form in PK-15 cells. The results showed that PCV2 infection was inhibited by HMGCR overexpression, whereas it was significantly increased in HMGCR-silenced cells and HMGCR inhibitor-treated cells. Moreover, there was a robust apoptotic response at 48 h post-infection (p.i.) in HMGCR-inactivated cells, and this response was significantly greater than that observed in PK-15 cells. A modest apoptotic response was also observed in HMGCR-silenced cells. Caspase-3 activity was also analysed in PCV2-infected cells at 48 h p.i. As expected, caspase-3 activity was significantly increased in HMGCR-inactivated and -silenced cells compared with PK-15 cells. PCV2 replication was dose-dependently increased in HMGCR-inactivated cells when treated with increasing amounts of caspase-3 inhibitor. Altogether, HMGCR was negatively associated with PCV2 infection and PCV2-induced apoptotic cell death. These data demonstrated that HMGCR can be used as a candidate target for PCV2 disease control and antivirus research. Furthermore, the cells generated in this study can be used to evaluate the potential effects of HMGCR on PCV2 replication.
authors.affiliation: Jilin Provincial Key Laboratory of Animal Embryo Engineering, College of Animal Sciences, Jilin University, Changchun, Jilin 130062, PR China.
authors.forename: Xin
authors.initials: X
authors.lastname: Yang
authors.affiliation: Jilin Provincial Key Laboratory of Animal Embryo Engineering, College of Animal Sciences, Jilin University, Changchun, Jilin 130062, PR China.
authors.forename: Hongsheng
authors.initials: H
authors.lastname: Ouyang
authors.affiliation: Jilin Provincial Key Laboratory of Animal Embryo Engineering, College of Animal Sciences, Jilin University, Changchun, Jilin 130062, PR China.
authors.forename: Fuwang
authors.initials: F
authors.lastname: Chen
authors.affiliation: Jilin Provincial Key Laboratory of Animal Embryo Engineering, College of Animal Sciences, Jilin University, Changchun, Jilin 130062, PR China.
authors.forename: Daxing
authors.initials: D
authors.lastname: Pang
authors.affiliation: Jilin Provincial Key Laboratory of Animal Embryo Engineering, College of Animal Sciences, Jilin University, Changchun, Jilin 130062, PR China.
authors.forename: Meichen
authors.initials: M
authors.lastname: Dong
authors.affiliation: Jilin Provincial Key Laboratory of Animal Embryo Engineering, College of Animal Sciences, Jilin University, Changchun, Jilin 130062, PR China.
authors.forename: Susu
authors.initials: S
authors.lastname: Yang
authors.affiliation: Jilin Provincial Key Laboratory of Animal Embryo Engineering, College of Animal Sciences, Jilin University, Changchun, Jilin 130062, PR China.
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Liu
authors.affiliation: Jilin Provincial Key Laboratory of Animal Embryo Engineering, College of Animal Sciences, Jilin University, Changchun, Jilin 130062, PR China.
authors.forename: Zhiyuan
authors.initials: Z
authors.lastname: Peng
authors.affiliation: Jilin Provincial Key Laboratory of Animal Embryo Engineering, College of Animal Sciences, Jilin University, Changchun, Jilin 130062, PR China.
authors.forename: Fei
authors.initials: F
authors.lastname: Wang
authors.affiliation: Jilin Provincial Key Laboratory of Animal Embryo Engineering, College of Animal Sciences, Jilin University, Changchun, Jilin 130062, PR China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Jilin Provincial Key Laboratory of Animal Embryo Engineering, College of Animal Sciences, Jilin University, Changchun, Jilin 130062, PR China.
authors.forename: Linzhu
authors.initials: L
authors.lastname: Ren
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002460:Cell Line; D018173:Circoviridae Infections / Q000201:enzymology / Q000662:veterinary / Q000821:virology; D017925:Circovirus / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology; D020868:Gene Silencing; D024581:Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating); D006903:Hydroxymethylglutaryl CoA Reductases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D013552:Swine; D013553:Swine Diseases / Q000201:enzymology / Q000473:pathology / Q000821:virology; D014774:Virulence; D014779:Virus Replication
chemical_list: D034741:RNA, Small Interfering; D006903:Hydroxymethylglutaryl CoA Reductases; D024581:Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating)