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Deciphering the Association of Epstein-Barr Virus and Its Glycoprotein M Peptide with Neuropathologies in Mice
Annu Rani1, Priyanka Patra1, Tarun Prakash Verma1
1Department of Biosciences and Biomedical Engineering, Indian Institute of Technology Indore, Indore, Madhya Pradesh 453552, India.
Abstract:
The reactivation of ubiquitously present Epstein-Barr virus (EBV) is known to be involved with numerous diseases, including neurological ailments. A recent in vitro study from our group unveiled the association of EBV and its 12-amino acid peptide glycoprotein M146-157 (gM146-157) with neurodegenerative diseases, viz., Alzheimer's disease (AD) and multiple sclerosis. In this study, we have further validated this association at the in vivo level. The exposure of EBV/gM146-157 to mice causes a decline in the cognitive ability with a concomitant increase in anxiety-like symptoms through behavioral assays. Disorganization of hippocampal neurons, cell shrinkage, pyknosis, and apoptotic appendages were observed in the brains of infected mice. Inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were found to be elevated in infected mouse brain tissue samples, whereas TNF-α exhibited a decline in the serum of these mice. Further, the altered levels of nuclear factor-kappa B (NF-kB) and neurotensin receptor 2 affirmed neuroinflammation in infected mouse brain samples. Similarly, the risk factor of AD, apolipoprotein E4 (ApoE4), was also found to be elevated at the protein level in EBV/gM146-157 challenged mice. Furthermore, we also observed an increased level of myelin basic protein in the brain cortex. Altogether, our results suggested an integral connection of EBV and its gM146-157 peptide to the neuropathologies.
Insights
Epstein-Barr virus (EBV) and its peptide gM146-157 induce cognitive decline and anxiety in mice, indicating a link to neurodegenerative diseases like Alzheimer's.
Area of Science:
- Neuroscience
- Immunology
- Virology
Background:
- Epstein-Barr virus (EBV) reactivation is linked to various diseases, including neurological conditions.
- Previous in vitro studies suggested a connection between EBV, its peptide gM146-157, and neurodegenerative diseases such as Alzheimer's disease (AD) and multiple sclerosis.
Purpose of the Study:
- To validate the association of EBV and its peptide gM146-157 with neurodegenerative pathologies at the in vivo level.
- To investigate the effects of EBV/gM146-157 exposure on cognitive function, anxiety, and neuropathological markers in a mouse model.
Main Methods:
- Mice were exposed to EBV/gM146-157.
- Behavioral assays were conducted to assess cognitive ability and anxiety-like symptoms.
- Brain tissue and serum were analyzed for neuronal integrity, inflammatory cytokines (TNF-α, IL-6), NF-kB, neurotensin receptor 2, apolipoprotein E4 (ApoE4), and myelin basic protein.
Main Results:
- EBV/gM146-157 exposure led to impaired cognitive function and increased anxiety in mice.
- Histopathological examination revealed hippocampal neuron disorganization, cell shrinkage, pyknosis, and apoptosis.
- Elevated levels of TNF-α and IL-6 were observed in infected brain tissue, alongside altered NF-kB and neurotensin receptor 2.
- Increased levels of AD risk factor ApoE4 and myelin basic protein were detected in challenged mice.
Conclusions:
- EBV and its gM146-157 peptide contribute to cognitive decline and anxiety-like behaviors in vivo.
- The study provides evidence for EBV-induced neuroinflammation and neuropathological changes, including neuronal damage and altered myelin.
- Results suggest a significant role for EBV and its peptide in the pathogenesis of neurodegenerative diseases.
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