Virus Demyelination

Abstract

A number of viruses can initiate central nervous system (CNS) diseases that include demyelination as a major feature of neuropathology. In humans, the most prominent demyelinating diseases are progressive multifocal leukoencephalopathy, caused by JC papovirus destruction of oligodendrocytes, and subacute sclerosing panencephalitis, an invariably fatal childhood disease caused by persistent measles virus. The most common neurological disease of young adults in the developed world, multiple sclerosis, is also characterized by lesions of inflammatory demyelination; however, the etiology of this disease remains an enigma. A viral etiology is possible, because most demyelinating diseases of known etiology in both man and animals are viral. Understanding of the pathogenesis of virus-induced demyelination derives for the most part from the study of animal models. Studies with neurotropic strains of mouse hepatitis virus, Theiler's virus, and Semliki Forest virus have been at the forefront of this research. These models demonstrate how viruses enter the brain, spread, persist, and interact with immune responses. Common features are an ability to infect and persist in glial cells, generation of predominantly CD8(+) responses, which control and clear the early phase of virus replication but which fail to eradicate the infection, and lesions of inflammatory demyelination. In most cases demyelination is to a limited extent the result of direct virus destruction of oligodendrocytes, but for the most part is the consequence of immune and inflammatory responses. These models illustrate the roles of age and genetic susceptibility and establish the concept that persistent CNS infection can lead to the generation of CNS autoimmune responses.

Parental Age, Family Size, and Risk of Multiple Sclerosis

“…8 Several viruses can cause diseases involving demyelination, including measles, human immunodeficiency virus (HIV), and the human T-cell lymphotropic virus type I. 23 Therefore, it is biologically plausible for MS, as a demyelinating disease, to have a viral etiology. Viruses associated with MS have included measles, 3 Epstein-Barr virus (infectious mononucleosis), 4 human herpes virus 6, 5 and mumps.…”

Acute Simian Varicella Virus Infection Causes Robust and Sustained Changes in Gene Expression in the Sensory Ganglia

“…Interestingly, these DEGs remained downregulated long after virus replication had ended, suggesting that SVV infection of the ganglia results in long-term changes in the ganglion transcriptome. Several of these genes were involved in myelination (MOBP, MAG, MBP, and PRG4), which suggested that SVV may lead to demyelination, as has been described for HSV-1 and -2 (149,150). Genes downregulated 14 dpi were involved in neuronal apoptosis, which may be another strategy that SVV utilizes to establish latency in the ganglia.…”

Pharmacological approaches to intervention in hypomyelinating and demyelinating white matter pathology

“…Immune mediators secreted by T cells and macrophages/microglia have been suggested to contribute to virally-induced demyelination due to dysregulation or death of oligodendrocyte lineage cells (Marro et al, 2014). These models are often considered alongside autoimmune-based models such as EAE, as they are useful for the characterization of infectious events leading to CNS immune responses (Baker and Amor, 2015; Fazakerley and Walker, 2003). Although EAE is powerful and remains most commonly used MS model, it is recognized that its limitations for MS therapy (Constantinescu et al, 2011) stem from a dependence on the artificial induction of the immune response (Mecha et al, 2013), unreliable predictability of treatments, a spinal cord preference over brain lesions, difficulty in analyzing remyelination of stochastic lesions and inconsistency of clinical functional progression (Ransohoff, 2012).…”