Differential Protein Analysis Of Infants Infected With Respiratory Syncytial Virus

Objective:Respiratory syncytial virus(RSV)infection is a major cause of lower respiratory tract infections in infants.To date,effective treatment against RSV infection is lacking.This study explores potential treatment options against RSV infection,via the identification of potential drug targets.As such,the study provides key insights into RSV diagnosis and aids with disease condition assessment.Methods:1.40 infants with bronchiolitis caused by RSV infection were recruited.These infants were diagnosed and treated in the Respiratory Department of Guangzhou Women and Children Medical Center from February to March 2019.They were grouped into acute phase and recovery phase groups according to their stage of RSV infection.In the meantime,20 healthy infants of the matching age and sex were recruited as the control group during their visits to the Health Examination Centre of the same hospital.2.Proteomics analysis was performed on the serum of recruited infants to identify differentially expressed protein(DEP).3.Candidate proteins were subsequently identified through functional enrichment,signaling pathways,and protein-protein interaction network analysis.4.Biomarkers for the treatment against RSV infection were validated as follows:a.The levels of inflammatory factors,vascular endothelial factors and candidate proteins for RSV infection in clinical samples were detected by enzyme-linked immunosorbent assay and Western blot.b.The RSV-infected mouse model was established,followed by the analysis of concentrations of inflammatory factors,vascular endothelial factors and candidate proteins in the mice using enzyme-linked immunosorbent assay,Western blot and immunohistochemistry.c.The concentration of several key rate-limiting enzymes in Glycolytic pathway in RSV infected patients and mice were tested by Enzyme-linked immunosorbent assay.Results:1.Through conducting the proteomics analysis,we found that 59 proteins were differentially expressed in the acute stage RSV infection group,when compared to the control group.Of these differentially expressed proteins,42 were up-regulated,and 17 were down-regulated.In the recovery phase group,we identified a total of 56 differentially expressed proteins,with 45 being up-regulated,and 11 being down-regulated,when compared to the control group.Through GO and KEGG analysis,we found that the glycolytic pathway is the most closely associated with RSV infection among all signal pathways.This suggests that the glycolytic pathway is related to RSV infection.The PPI network analysis shows that Peroxiredoxin 2(PrDX2),triose-phosphate isomerase-1(TPI1),bi-phosphoglycerate mutase(BPGM),and Cofilin 1(CFL1)were located in the key nodes in the PPI network.Among them,TPI1 and BPGM are related to the glycolysis pathway,PrDX2 is related to the regulation of reactive oxygen species(ROS)detoxification pathway,and CFL1 is related to the ephrin signaling pathway.2.The concentrations of inflammation factors,such as beta interleukins-1(IL-1 beta),interleukin 6(IL-6)and tumor necrosis factor alpha(TNF alpha),and vascular endothelial damage factors including von Willebrand factor(VWF),blood clots regulatory proteins(TM)and endothelial nitric oxide synthase(eNOS)in children and mice infected by RSV were higher in the acute and recovery stages compared with those in the control group,which were statistically significant;The recovery period was lower than the acute period,and the difference was statistically significant.3.The levels of BPGM,TPI1,PrDX2 and CFL1 proteins in RSV-infected clinical samples and RSV-infected mice were significantly up-regulated in the acute and recovery stages compared with those in the control group,with statistical differences.The recovery period was lower than the acute period,and the difference was statistically significant.4.The contents of metabolites in glycolytic pathway,such as pyruvate and lactic acid in children and mice infected with RSV,were significantly increased in acute phase and recovery period compared with those in the control group,with statistical differences;The recovery period was lower than the acute period,and the difference was statistically significant.Conclusion:1.Glycolytic metabolic pathway may be involved in RSV infection.2.The levels of BPGM,TPI1,PRDX2 and CFL1 proteins were significantly higher in RSV-infected patients and RSV-infected mice compared with control group.They may be potential drug targets for the treatment of RSV infection.