Research Projects

Non-polio enteroviruses (NPEV) are increasing being reported as common cause of neurological illnesses in children across the world. Neurological complications due to enteroviruses (EVs) have become notable features of EV-71 outbreaks and were the primary cause of death, however the biological determinants of different pathological features of EV infection are poorly understood. Reports from autopsy studies from EV-A71 infection of CNS have shown inflammation in various regions of brain including brainstem and anterior horn cells of spinal cord. However, the localization of the viral antigens/ RNA was restricted and could not be well correlated with the extent and severity of inflammation, therefore, two major mode of neuro-destruction were proposed in infected cells, which include: Viral cytolysis mediated neuronophagia/ neurodegeneration, and Potential immune-mediated tissue injury. Despite a consensus on neuro-destructive pathogenesis of EV-A71, there are a burning question that remain unaddressed: What is the selection bottleneck in respiratory and digestive tract tissues that is required to be overcome for switching the viral tropism from aero-digestive to neurotropism? Herein we are using the neurovascular organoid models to study the pathogenesis of neuroinvasive enterovirus infection. The viral isolates form intestinal organoids will be used to infect neurovascular organoids to represent the intestine-to-CNS switch. High throughput transcriptome analysis of the infected organoid will allow us to analyze different potential host and viral factors and their interactions involved in a neuroinvasive vis a vis non neuroinvasive disease. Various deregulated pathways and/proteins can also be identified which can be used as potential surrogate markers/ prognostic markers to identify enteroviral etiology in neuroinvasive diseases. In the present study we propose to use single cell RNA sequencing (sc-RNA-seq) to identify the presence of specific cells in 3-D NVOs which are targeted by EVs. Thus this study will help in filling the gaps about the knowledge of neurotropism and neuroinvasion of enterovirus in terms of viral and host factors.