Metabolic Profiles in Cell Lines Infected with Classical Swine Fever Virus

Abstract

Viruses require energy and biosynthetic precursors from host cells for replication. An understanding of the metabolic interplay between classical swine fever virus (CSFV) and host cells is important for exploring the complex pathological mechanisms of classical swine fever (CSF). In the current study, and for the first time, we utilized an approach involving gas chromatography coupled with mass spectrometry (GC-MS) to examine the metabolic profiles within PK-15 and 3D4/2 cells infected with CSFV. The differential metabolites of PK-15 cells caused by CSFV infection mainly included the decreased levels of glucose 6-phosphate [fold change (FC) = −1.94)] and glyceraldehyde-3-phosphate (FC = −1.83) during glycolysis, ribulose 5-phosphate (FC = −1.51) in the pentose phosphate pathway, guanosine (FC = −1.24) and inosine (FC = −1.16) during purine biosynthesis, but the increased levels of 2-ketoisovaleric acid (FC = 0.63) during the citrate cycle, and ornithine (FC = 0.56) and proline (FC = 0.62) during arginine and proline metabolism. However, metabolite changes caused by CSFV infection in 3D4/2 cells included the reduced glyceraldehyde-3-phosphate (FC = −0.77) and pyruvic acid (FC = −1.42) during glycolysis, 2-ketoglutaric acid (FC = −1.52) in the citrate cycle, and the elevated cytosine (FC = 2.15) during pyrimidine metabolism. Our data showed that CSFV might rebuild cellular metabolic programs, thus aiding viral replication. These findings may be important in developing targets for new biomarkers for the diagnosis and identification of enzyme inhibitors or metabolites as antiviral drugs, or screening viral gene products as vaccines.

Serum Lipidomics Analysis of Classical Swine Fever Virus Infection in Piglets and Emerging Role of Free Fatty Acids in Virus Replication in vitro

“…Our previous work has confirmed that CSFV rebuild cellular metabolic programs in vitro , thus aiding viral replication (Hongchao et al, 2017; Wenjie et al, 2017). However, systematic changes in lipid metabolites in CSFV-infected cells remain unknown.…”

“…It is well-known that viruses alter host metabolism, especially lipid metabolism, to facilitate their infection and replication (Heaton and Randall, 2011). Like other members of the Flaviviridae family, CSFV can also cause cellular metabolic disorders and lead to a series of pathological reactions, such as high fever, multiple hemorrhage, leukopenia and inflammation (Kleiboeker, 2002; Lohse et al, 2012; Hongchao et al, 2017). In the current study, we provided for the first time observations on the lipids changes in the serum of CSFV-infected piglets based on UHPLC-QTOF-MS, which might provide suitable targets for drug intervention and therapeutic vaccines.…”

“…The cells were cultured at 37°C with 5% CO 2 . The virulent CSFV strain Shimen was used in the present study and tittered as described previously (Hongchao et al, 2017). All cells with 80% confluences in cell culture plates were infected in serum-free DMEM medium with CSFV at a multiplicity of infection (MOI) of 1 for 2 h, after which the medium was replaced with complete DMEM or RPMI 1640 containing 2% FBS.…”

LDHB inhibition induces mitophagy and facilitates the progression of CSFV infection

“…Meanwhile, lactate participates in mitochondrial oxidative activity in cultured CHO cells and that LDHB localizes to the mitochondria [25,26]. We and other researchers have found that CSFV infection promoted lactate release and inhibits pyruvate release [38,39]. Based on these results, we hypothesized that LDHB may also elicit an effect on mitophagy.…”

Dimethylaminomicheliolide (DMAMCL) Suppresses the Proliferation of Glioblastoma Cells via Targeting Pyruvate Kinase 2 (PKM2) and Rewiring Aerobic Glycolysis

“…The quality of the models is described by the R 2 X or R 2 Y and Q 2 values. Differential metabolites were determined by the combination of variable importance in the projection (VIP) value (>1) of the OPLS-DA model and the p -values (<0.05) from two-tailed student's t -tests on normalized peak intensities (31).…”