TY - JOUR
T1 - Pathway Analysis of Proteomics Profiles in Rabies Infection
T2 - Towards Future Biomarkers?
AU - Mehta, Shraddha
AU - Sreenivasamurthy, Sreelakshmi
AU - Banerjee, Shefali
AU - Mukherjee, Sandeepan
AU - Prasad, Keshava
AU - Chowdhary, Abhay
N1 - Publisher Copyright:
© Copyright 2016, Mary Ann Liebert, Inc. 2016.
PY - 2016/2/1
Y1 - 2016/2/1
N2 - 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.
AB - 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.
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U2 - 10.1089/omi.2015.0137
DO - 10.1089/omi.2015.0137
M3 - Article
C2 - 26871867
AN - SCOPUS:84958639918
SN - 1536-2310
VL - 20
SP - 97
EP - 109
JO - OMICS A Journal of Integrative Biology
JF - OMICS A Journal of Integrative Biology
IS - 2
ER -