Microparticles are involved in the pathogenesis of Japanese encephalitis virus infection

Title : Microparticles are involved in the pathogenesis of Japanese encephalitis virus infection

Abstract:

Increases in the circulation of microparticles (MPs) indicate the progression of inflammation, immune cell activation, and the involvement of cell death pathways. Herein, in the current study, we investigated the role of MPs in Japanese Encephalitis Virus (JEV) infection. We found that macrophage cells are susceptible to JEV infection, leading to a significant increase in macrophage-derived MPs in the conditioned media compared to control macrophage cells (p<0.05). JEV-infected MPs contain JEV nucleotides and further activate naïve macrophage cells, thereby inducing proinflammatory cytokine release. A significant increase was found in nitric oxide (p<0.01) and TNF-α (p<0.05) expression in macrophages treated with JEV-infected MPs. Notably, neutralizing MPs through heat inactivation or by blocking MPs receptors (such as annexin) significantly mitigates the JEV-induced inflammatory response of nitric oxide (p<0.01) and TNF-α (p<0.01) and reduces the JEV copy numbers by 4-fold. Overall result shows MPs involve in JEV pathogenesis. The identification of the important roles played by MPs in JEV pathogenesis and the development of inflammation will support the novel therapeutic approach development to control acute JEV infection.

Audience Takeaway Notes: 

• Microparticles are submicron membrane vesicles shed from the cell surface of both healthy and virus infected cells.
• This work demonstrates how Microparticles alter the characteristics of cells exposed to them, thus constituting a system of cell-cell communications, complementing cell-cell contacts and communication by soluble factors like cytokines.
• The experimental result concludes that Microparticles released by JEV infected cells contain virions, are endocytosed by naive cells, and lead to a progressive inflammation. Control or neutralization of Microparticle can inhibit JEV infection.

Biography:

Dr. Alok Kumar is an Additional professor at Department of Molecular Medicine and Biotechnology in Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGI), Lucknow. Dr. Kumar conducted postdoctoral work training and studied the role of neuroinflammation in CNS injury at the Center for Shock, Trauma and Anaesthesiology Research (STAR-ORC), University of Maryland School of Medicine, Baltimore, Maryland, USA. He joined SGPGI as faculty in 2018. Dr. Kumar has authored or co-authored several peer-reviewed publications. His work has garnered numerous grants and awards, including the Ramalingaswami fellowship award from Department of Biotechnology (DBT, New Delhi) for research in Japanese encephalitis brain viral infection, Prof. E. Vijayan Award in Neuroscience for best oral presentation of the paper, first place and best poster award in National Capital Area TBI Research Symposium at National Institutes of Health (NIH), Bethesda, USA, scored among top twenty best research fellows at National Neurotrauma Conference in Phoenix, USA and many travel awards from National Neurotrauma Symposium, USA, Federation of European Neuroscience Societies (FENS), Belgium and International Society for Neurochemistry (ISN), USA. His contribution in scientific field for "CNS injury and immune cell activation" were well acknowledged and highlighted in number of USA media reports for instance "Mystery brain particles and their role in seeding neuroinflammation", 2017; “Do spinal cord injuries cause subsequent brain damage?“ 2014; among others. He is an ad-hoc reviewer of several international neuroinfectious diseases, neurotrauma and neuroscience journals. He has been a member of the National Neurotrauma Society (NNS) USA, the Society for Neuroscience (SFN), USA, and International Brain Research Organization (IBRO), France.