| Rabies virus is a highly neurotropic virus that invades the central nervous system(CNS),where it causes an acute infection and brain dysfunction.Rabies viruses continue to pose some of the greatest threats to human and animal health.Viruses replicate and proliferate in host cel s while continuously adjusting to and modulat ing the host environment.Proteomic studies of the host upon viral infection have delineated the molecular interactions between the virus and the host,thus providing hints for the detection,diagnosis,and therapeutics of infectious diseases.It is well established now that neuronal dysfunction rather than structural damage may be responsible for the development of rabies.In order to explore the underlying mechanisms in rabies virus(RABV)and synaptic dysfunctions,we have used quantitative proteomics(Neno LC-MS/MS)to investigate the synaptosome proteomics of mouse hippocampus among street strain rabies virus infected compared to uninfec ted mice.Synaptosome samples from mice hippocampus were isolated and confirmed by Western blot and transmission electron microscopy.Synaptosome protein content changes were quantitatively detected by Nano-LC–MS/ MS.Protein functions were classified by the Gene Ontology(GO)and KEGG pathway.PSICQUIC was used to create a network.MCODE algorithm was applied to obtain subnetworks.Of these protein changes,45 were upregulated and 14 were downregulated following RABV infection relative to non-infected(mock)synaptosomes.28 proteins were unique to mock treatment and 12 were unique to RABV treatment.Proteins related to metabolis m and synaptic vesicle showed the most changes in expression levels.Furthermore,protein–protein interaction(PPI)networks revealed that several key biologic a l processes related to synaptic functions potentially were modulated by RABV,includ ing energy metabolism,cytoskeleton organization,and synaptic transmission.There exists complex interaction between host and virus upon protein regulation.Based on quantitative proteomics we studied the expression alteration of proteins in synaptosome of mouse hippocampus before and after RABV infection,which hints that RABV affect the physiological function of synaptosomes by changing the expression of proteins in synaptosomes of host.These data will be useful for better understanding of neuronal dysfunction of rabies and provide the foundation for future research. |
