Comparative Proteomic Profiling: Cellular Metabolisms Are Mainly Affected in Senecavirus A-Inoculated Cells at an Early Stage of Infection

Abstract

Senecavirus A (SVA), also known as Seneca Valley virus, belongs to the genus Senecavirus in the family Picornaviridae. SVA can cause vesicular disease and epidemic transient neonatal losses in pigs. This virus efficiently propagates in some non-pig-derived cells, like the baby hamster kidney (BHK) cell line and its derivate (BSR-T7/5). Conventionally, a few proteins or only one protein is selected for exploiting a given mechanism concerning cellular regulation after SVA infection in vitro. Proteomics plays a vital role in the analysis of protein profiling, protein-protein interactions, and protein-directed metabolisms, among others. Tandem mass tag-labeled liquid chromatography-tandem mass spectrometry combined with the parallel reaction monitoring technique is increasingly used for proteomic research. In this study, this combined method was used to uncover separately proteomic profiles of SVA- and non-infected BSR-T7/5 cells. Furthermore, both proteomic profiles were compared with each other. The proteomic profiling showed that a total of 361 differentially expressed proteins were identified, out of which, 305 and 56 were upregulated and downregulated in SVA-infected cells at 12 h post-inoculation, respectively. GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment analyses showed that cellular metabolisms were affected mainly in SVA-inoculated cells at an early stage of infection. Therefore, an integrated metabolic atlas remains to be explored via metabolomic methods.

Senecavirus A- and Non-Infected Cells at Early Stage of Infection: Comparative Metabolomic Profiles

“…Fluorescence became increasingly bright from 6 to 9 hpi, and was relatively stable after 9 hpi (Liu et al, 2020a). SVA generally induces unobservable CPE on cell monolayers within 12 hpi, during which the virus-infected cells, however, underwent significant variation in several metabolic pathways, like carbon, purine and pyrimidine metabolisms, as evidenced by our recent report concerning proteomic profiling for SVA-infected cells (Liu et al, 2021b). SVA infection triggers a variety of metabolic and biochemical changes in its host cells through virus-specific or -nonspecific mechanisms (Fernandes et al, 2019;Hou et al, 2019;Wen et al, 2019;Li et al, 2020).…”

“…Host nucleotides and their derivatives are important small molecules, playing a crucial role in cellular metabolism, such as signal transduction, and synthesis of genetic materials (Tian et al, 2019). In our recent proteomics report, the pyrimidine metabolism was also demonstrated to have the lowest p value, and however the highest number of significantly differential metabolites were enriched into the purine metabolism (Liu et al, 2021b). Such a slight difference in metabolic profiles between two omics studies might be attributed to distinct methods of experimentation and (or) analysis.…”

“…In the present study, the LC-MS/MS method was used to analyze comparatively metabolomic profiles between SVA-and non-infected BSR-T7/5 cells. The reason why we conducted this study was that our earlier research had preliminarily shown cellular metabolisms, mainly affected in SVA-inoculated cells at the early stage of infection (Liu et al, 2021b). The virus used here was the rescued SVA by means of reverse genetics.…”

“…Integrated omics can assist on deciphering complex networks in vitro or in vivo, and especially on unveiling the interaction among bio-relevant molecules to affect disease outcome (Rosa-Fernandes et al, 2019). Besides our recent proteomics study on SVA-infected cells (Liu et al, 2021b), Wang et al (2020) had reported earlier a transcriptomic profile of SVA-infected pig kidney cells (Wang et al, 2020).…”

“…Since then, a variety of viruses have been demonstrated to alter multiple metabolic pathways in cells, like glycolysis and fatty acid synthesis, and have expanded the number of cellular metabolites (Birungi et al, 2010;Ritter et al, 2010;Hollenbaugh et al, 2011;Delgado et al, 2012;Sanchez et al, 2017;Tian et al, 2019;Li et al, 2021;Nunes et al, 2021;Pant et al, 2021;Wang et al, 2021). We have constructed a wild-type SVA (CH-LX-01-2016) using reverse genetics (Liu et al, 2021a), and more recently have revealed a proteomic profile of BSR-T7/5 cells inoculated with this virus at 12 hpi (Liu et al, 2021b). In the present study, in order to uncover its metabolomic profile, the SVA-inoculated BSR-T7/5 cell monolayer was collected at 12 hpi for assay via liquid chromatography-tandem mass spectrometry (LC-MS/MS).…”