title: Pathway Analysis of Proteomics Profiles in Rabies Infection: Towards Future Biomarkers?
abstract: Rabies is a zoonotic viral disease that invariably leads to fatal encephalitis, which can be prevented provided post-exposure prophylaxis is initiated timely. Ante-mortem diagnostic tests are inconclusive, and rabies is nontreatable once the clinical signs appear. A large number of host factors are responsible for the altered neuronal functions observed in rabies; however their precise role remains uninvestigated. We therefore used two-dimensional electrophoresis and mass spectrometry analysis to identify differentially expressed host proteins in an experimental murine model of rabies. We identified 143 proteins corresponding to 45 differentially expressed spots (p < 0.05) in neuronal tissues of Swiss albino mice in response to infection with neurovirulent rabies strains. Time series analyses revealed that a majority of the alterations occur at 4 to 6 days post infection, in particular affecting the host's cytoskeletal architecture. Extensive pathway analysis and protein interaction studies using the bioinformatic tools such as Ingenuity Pathway Analysis and STRING revealed novel pathways and molecules (e.g., protein ubiquitination) unexplored hitherto. Further activation/inhibition studies of these pathway molecular leads would be relevant to identify novel biomarkers and mechanism-based therapeutics for rabies, a disease that continues to severely impact global health.
authors.affiliation: 1 Department of Virology and Immunology, Haffkine Institute for Training , Research and Testing, Mumbai, India .
authors.forename: Shraddha
authors.initials: S
authors.lastname: Mehta
authors.affiliation: 2 Institute of Bioinformatics , International Technology Park, Bangalore, India .|3 Manipal University , Madhav Nagar, Manipal, India .
authors.forename: Sreelakshmi
authors.initials: S
authors.lastname: Sreenivasamurthy
authors.affiliation: 1 Department of Virology and Immunology, Haffkine Institute for Training , Research and Testing, Mumbai, India .
authors.forename: Shefali
authors.initials: S
authors.lastname: Banerjee
authors.affiliation: 1 Department of Virology and Immunology, Haffkine Institute for Training , Research and Testing, Mumbai, India .
authors.forename: Sandeepan
authors.initials: S
authors.lastname: Mukherjee
authors.affiliation: 2 Institute of Bioinformatics , International Technology Park, Bangalore, India .|4 NIMHANS-IOB Proteomics and Bioinformatics Laboratory, Neurobiology Research Centre, National Institute of Mental Health and Neurosciences , Bangalore, India .
authors.forename: Keshava
authors.initials: K
authors.lastname: Prasad
authors.affiliation: 1 Department of Virology and Immunology, Haffkine Institute for Training , Research and Testing, Mumbai, India .
authors.forename: Abhay
authors.initials: A
authors.lastname: Chowdhary
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000378:metabolism* / Q000821:virology; D054884:Host-Pathogen Interactions; D051379:Mice; D060066:Protein Interaction Maps; D020543:Proteome / Q000378:metabolism*; D040901:Proteomics; D011818:Rabies / Q000378:metabolism*; D011820:Rabies virus / Q000502:physiology; D015398:Signal Transduction; D053719:Tandem Mass Spectrometry
chemical_list: D015415:Biomarkers; D020543:Proteome