**Abstract**

Meningoencephalomyelitis emanates under the umbrella relating inflammatory changes of the Central Nervous System (CNS). Meningitis denotes inflammation in the meningeal layers, encephalitis is an acute diffuse inflammation of the brain, and inflammation in the spinal cord is denoted as myelitis. These can be interrelated or independent of each other depending on the etiology. The entire mechanism of meningoencephalomyelitis is governed by an acute innate inflammatory branch followed by a chronic progressive, adaptive branch of immunity with clinical signs like hyperthermia, weight loss, hypoxia, leukocytosis. This book chapter will focus on viral-induced meningitis, encephalitis, and myelitis. Thirty years of experience working with a murine-β-coronavirus (m-CoV); Mouse hepatitis virus (MHV)-A59 induced experimental model system provided us a thorough understanding of neuroglial cell-mediated acute neuroinflammation, denoted by the accumulation of leukocyte-common-antigen (LCA) positive or CD45+ leukocytes in perivascular infiltrates referred to as perivascular cuff formation and microglial nodules in the brain parenchyma, which mimics specific pathology of human neurological disease multiple sclerosis (MS). Additionally, in this chapter, we summarized the role of CNS resident microglial activation and its interaction with peripheral migratory T cells in mounting neuropathogenesis and host immunity in different families of neurotrophic encephalomyelitis viruses that cause CNS inflammation.

**Keywords:** meningioencephalomyelitis, demyelination, axonal loss, murine-β-coronavirus (m-CoV), neuroinflammation, multiple sclerosis (MS)

## **1. Introduction**

Encephalitis is a pathological entity that refers to the inflammation of the *encephalon* or the brain parenchyma due to infection, autoimmunity, and brain injury. It is a rare medical condition with clinically serious consequences ranging from headaches, fever, seizures, permanent disability, and brain damage. Encephalitis majorly affects infants and the elderly above the age of 65, whereas, the incidence is transitional in the youth and is of significant public health importance because of the associated morbidity and mortality [1]. It results in varied clinical symptoms, such as mild fever and headaches to severe cognitive impairment accompanied by loss of physical vigor

and unconsciousness or even life-threatening symptoms that can result in permanent brain damage [2, 3]. It is believed that the severe inflammation associated with encephalitis causes swelling in the brain, which in turn gives rise to headaches, stiff neck, mental confusion, and even seizures [1, 4]. Though cases are recognized in all populations and ages, pediatric populations, young adults, and especially males have a higher propensity to encephalitis [5–7].

Infection by a virus is the most common and important cause of encephalitis [8]. Virus infections can also cause aseptic meningitis and myelitis [9, 10]. Research on viral encephalitis has gained much momentum with the recognition of encephalitis in human immunodeficiency virus (HIV) infection of the CNS and the emerging viruses such as West Nile virus (WNV), Nipah virus, and severe acute respiratory syndrome viruses (SARS-CoV and SARS-CoV-2) [11]. Members of several virus families like flaviviruses, paramyxoviruses, alphaviruses, bunyaviruses, orthomyxoviruses, arenaviruses, enteroviruses, rhabdoviruses, and astroviruses are also known to cause encephalitis [12].

Viruses may directly enter into the CNS or replicate away from the CNS at first and gain entry to the CNS through various routes [13, 14]. Local factors, like pH, mucosal immune responses, or the integrity of skin and mucosal barriers, govern the entry of the virus into the CNS and resultant encephalitis. Virus entry and replication activate the CNS resident immune cells, which, together with peripheral leukocytes, induce host immune response and promote encephalitis and neuroinflammation, resulting in multiple changes to the CNS physiology [15]. Histopathologically, characteristic microglial nodule formation, i.e., the accumulation of activated microglia in the brain parenchyma and the perivascular cuff formation, is observed in encephalitic brains [16–18]. Once the virus clears, the acute behavioral symptoms are resolved; however, long-term psychiatric, neurocognitive, and degenerative issues persist due to the ongoing immune responses in the CNS even after pathogen clearance [18, 19].

Interestingly, people infected with neurotropic viruses may not always develop encephalitis, indicating that host cell factors may play a critical role in regulating the outcome of the disease process. While mounting shreds of evidence are available to understand these host factors, limited information is available to understand the genomic control of the pathogenic properties and host factors that mediate a balance between neurovirulence and neuroprotection. Host cell response pathways like UPR and ER stress and oxidative stress may alter due to robust viral replication and intracellular assembly, causing imbalance between reactive oxygen species and antioxidants. These are governed by a battery of cellular mediators like DJ-1, Nrf-2, catalase, HMOX, MMPs, NADPH oxidase, cytokines, chemokines, and secondary messengers. These mediators are either CNS resident proteins or may be produced by the CNS resident neuro-glial cells like microglia, astrocytes, endothelial cells, and peripherally derived leukocytes that enter the CNS upon inflammation and breaching of the blood-brain barrier [13]. The nexus of these immune-inflammatory mediators with endogenous host proteins are well studied for ages in mounting host immunity. The question lies in whether host immunity plays a protective or pathogenic role.

Moreover, understanding the inflammatory mechanisms of meningioencephalomyelitis is a challenge in human patients due to the unavailability of the high throughput data from non-invasive techniques like MRI, fMRI, CT, and detailed invasive histopathological data from punched-biopsy/autopsy tissues. Thus, a thorough understanding of the cellular factors ranging from genomic control of pathogenic properties to viral host factors and immunomodulatory effects requires cause-effect

### *Neurotropic Virus-Induced Meningoencephalomyelitis DOI: http://dx.doi.org/10.5772/intechopen.102674*

relationship experimental animal models/systems that can provide detailed insight into the disease process instrumental in the diagnosis and designing therapeutics. Though the use of mouse models to understand human disease has its limitations, critical pathological features of encephalitis can be efficiently reproduced in viralinduced experimental models. This book chapter will majorly summarize studies on viral encephalitis and its consecutive neuroinflammatory demyelination and axonal loss.
