Quantitative proteomics leads to identify dog brain proteins involved in rabies virus infection: implication in understa

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ORIGINAL ARTICLE

Quantitative proteomics leads to identify dog brain proteins involved in rabies virus infection: implication in understanding viral pathophysiology Suchismita Behera1 · Rajesh Raghunath Pharande2 · R. Rajendra Reddy1 · Sharmila B. Majee2 · Sandeepan Mukherjee3 · Amol Ratnakar Suryawanshi1  Received: 22 July 2020 / Revised: 5 October 2020 / Accepted: 16 October 2020 © Springer Nature Singapore Pte Ltd. 2020

Abstract Rabies is a neglected tropical disease caused by the rabies virus (RABV) and it is mostly transmitted to humans by dogs. However, knowledge about host factors and their role in RABV infection in dogs is still limited. This is the first study to identify differentially expressed dog brain proteins involved in naturally occurring rabies virus infection using iTRAQ-based proteomics approach. Here, we have reported 19 differentially expressed proteins (DEPs) in RABV infected dog brain compared to controls and some of these proteins are the first time reported. GO annotation revealed their involvement in various molecular functions and also their participation in cellular processes, biological regulation, and metabolic processes. Further, ingenuity pathway analysis (IPA) predicted the major protein network showing the connection of 13 DEPs and their role in some of the canonical pathways. IPA analysis also predicted their involvement in neurological disease, organismal injury and abnormalities, psychological disorders. Proteomics data were successfully validated at gene expression levels by qRT-PCR for five DEPs including two down-regulated proteins namely DDX3X and SNCB and three up-regulated proteins namely KCTD12, DLA-64 and IgSF. This study provides the list of molecules involved in RABV infection and gives some insight into the molecular pathophysiology involved in this infection. This also suggests that DE proteins like DDX3X may have importance in RABV replication similar to other viruses. However, further experiments are required to confirm the role of these proteins in the molecular mechanism of RABV infection. Keywords  Rabies · Proteomics · iTRAQ · IPA

Introduction Suchismita Behera and Rajesh Raghunath Pharande equally contributed and are Joint first authors. Electronic Supplementary Material  The online version of this article (https​://doi.org/10.1007/s4248​5-020-00051​-w) contains supplementary material, which is available to authorized users. * Rajesh Raghunath Pharande [email protected] * Amol Ratnakar Suryawanshi [email protected] 1



Clinical Proteomics, Institute of Life Sciences (DBT), Bhubaneswar, Odisha, India

2



Department of Microbiology, Mumbai Veterinary College, Mumbai, India

3

Department of Virology and Immunology, Haffkine Institute, Mumbai, India



Rabies is a zoonotic viral disease caused by rabies virus (RABV) and this belongs to the family Rhabdoviridae, genus Lyssavirus. According to WHO estimates, rabies occurs in more than 150 countries including 59,000 human deaths worldwide every year with 60% cases being reported in India (Hampson et al