Identification of ligand receptor interactions across blood brain barrier in viral neuro-pathogenesis.
Team: Dr. Shashikant Vaidya (PI) & Ms. Durga Bethala (DST-INSPIRE-SRF)
Funding Agency: Department of Science and Technology, Govt. of India
Duration: March 2017- Jan. 2024

Abstract:
More than 500 million people worldwide are infected each year by any of the four-dengue virus (DENV) serotypes. Dengue serotype 2 (DENV 2) is most predominant in India and other South Asian countries. The clinical spectrum caused during dengue infections is wide and some patients may develop neurological alterations during or after the infection. Clinical evidences suggests that blood brain barrier (BBB) may be compromised during DENV infection; however, it is not clear whether the damage is due to the infection per se or to the inflammatory response activated by the BBB cells. Other neurotropic flaviviruses such as Japanese encephalitis virus (JEV) are also known for neurological damage. JEV uses the bloodstream to enter nerve tissue where it infects cells of the neurovascular unit. Another neurotropic virus like rabies virus (RABV) chooses the retro-grade axonal route to infect the neuronal cells. Both JEV and RABV affect the cells of neurovascular unit in different ways resulting into BBB damage, glial activation and tissue inflammation. Our aim is to study pattern of DENV infection to BBB, compared with other neurotropic viruses like JEV and RABV using in vitro model. In our study, we observed that the BBB is dysregulated by superinfecting DENV2 activated murine macrophage (RAW264.7) on murine endothelial cells (BEnd3) rather upon direct virus infection.

 

Quantitative phosphoproteome profiling of circulating influenza virus strains in Mumbai region.
Team: Dr. Shashikant Vaidya (PI) and Ms. Pinky Singh (Ph. D. Student)
Funding Agency: Haffkine Institute
Duration: December 2017 to January 2025

Abstract:
Influenza viruses a major human pathogen whose genotypic diversity results in unpredictable pandemics and epidemics. Although annual influenza epidemics affect around 10% of the global population, current treatment options are limited and development of new antivirals is needed. Elucidation of host factors required during virus infection provides information not only on the signalling pathways involved but also on the identification of novel drug targets. Quantitative phosphoproteomic will help in revealing the unique phosphoproteome dynamics that occur in the host cell within minutes of influenza virus infection. In this study, Influenza virus isolates would be subjected to PCR for amplification of gene sequences as per WHO primer pairing for quantifying relative viral load. Quantitative phosphoproteomic analysis of human lung carcinoma, epithelial cell line (A549) infected with influenza viruses will be performed at varying time intervals. Harvested cells will be subjected for TEM and flow based studies followed by iTRAQ labelling. Identification and quantitative analysis of iTRAQ-labelled phosphopeptides will be performed using LC–MS/MS.