Raman
spectroscopy can be used as a tool to study virus entry and
pathogen-driven manipulation of the host efficiently. To date, Epstein–Barr
virus (EBV) entry and altered biochemistry of the glial cell upon
infection are elusive. In this study, we detected biomolecular changes
in human glial cells, namely, HMC-3 (microglia) and U-87 MG (astrocytes),
at two variable cellular locations (nucleus and periphery) by Raman
spectroscopy post-EBV infection at different time points. Two possible
phenomena, one attributed to the response of the cell to viral attachment
and invasion and the other involved in duplication of the virus followed
by egress from the host cell, are investigated. These changes corresponded
to unique Raman spectra associated with specific biomolecules in the
infected and the uninfected cells. The Raman signals from the nucleus
and periphery of the cell also varied, indicating differential biochemistry
and signaling processes involved in infection progression at these
locations. Molecules such as cholesterol, glucose, hyaluronan, phenylalanine,
phosphoinositide, etc. are associated with the alterations in the
cellular biochemical homeostasis. These molecules are mainly responsible
for cellular processes such as lipid transport, cell proliferation,
differentiation, and apoptosis in the cells. Raman signatures of these
molecules at distinct time points of infection indicated their periodic
involvement, depending on the stage of virus infection. Therefore,
it is possible to discern the details of variability in EBV infection
progression in glial cells at the biomolecular level using time-dependent in vitro Raman scattering.
The neurotropic potential of the Epstein-Barr virus (EBV) was demonstrated quite recently; however, the mechanistic details are yet to be explored. Therefore, the effects of EBV infection in the neural milieu remain underexplored. Previous reports have suggested the potential role of virus-derived peptides in seeding the amyloid-β aggregation cascade, which lies at the center of Alzheimer's disease (AD) pathophysiology. However, no such study has been undertaken to explore the role of EBV peptides in AD. In our research, ∼100 EBV proteins were analyzed for their aggregation proclivity in silico using bioinformatic tools, followed by the prediction of 20S proteasomal cleavage sites using online algorithms NetChop ver. 3.1 and Pcleavage, thereby mimicking the cellular proteasomal cleavage activity generating short antigenic peptides of viral origin. Our study reports a high aggregate-forming tendency of a 12-amino-acid-long ( 146 SYKHVFLSAFVY 157 ) peptide derived from EBV glycoprotein M (EBV-gM). The in vitro analysis of aggregate formation done using Congo red and Thioflavin-S assays demonstrated dose-and timedependent kinetics. Thereafter, Raman spectroscopy was used to validate the formation of secondary structures (α helix, β sheets) in the aggregates. Additionally, cytotoxicity assay revealed that even a low concentration of these aggregates has a lethal effect on neuroblastoma cells. The findings of this study provide insights into the mechanistic role of EBV in AD and open up new avenues to explore in the future.
The gut–brain axis is a bidirectional communication network connecting the gastrointestinal tract and central nervous system. The axis keeps track of gastrointestinal activities and integrates them to connect gut health to higher cognitive parts of the brain. Disruption in this connection may facilitate various neurological and gastrointestinal problems. Neurodegenerative diseases are characterized by the progressive dysfunction of specific populations of neurons, determining clinical presentation. Misfolded protein aggregates that cause cellular toxicity and that aid in the collapse of cellular proteostasis are a defining characteristic of neurodegenerative proteinopathies. These disorders are not only caused by changes in the neural compartment but also due to other factors of non-neural origin. Mounting data reveal that the majority of gastrointestinal (GI) physiologies and mechanics are governed by the central nervous system (CNS). Furthermore, the gut microbiota plays a critical role in the regulation and physiological function of the brain, although the mechanism involved has not yet been fully interpreted. One of the emerging explanations of the start and progression of many neurodegenerative illnesses is dysbiosis of the gut microbial makeup. The present understanding of the literature surrounding the relationship between intestinal dysbiosis and the emergence of certain neurological diseases, such as Alzheimer's disease, Parkinson’s disease, Huntington's disease, and multiple sclerosis, is the main emphasis of this review. The potential entry pathway of the pathogen-associated secretions and toxins into the CNS compartment has been explored in this article at the outset of neuropathology. We have also included the possible mechanism of undelaying the synergistic effect of infections, their metabolites, and other interactions based on the current understanding.
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