Experimental models of virus‐induced demyelination of the central nervous system

Canto, Mauro C. Dal; Rabinowitz, Stanley G.

doi:10.1002/ana.410110202

Cited by 169 publications

(64 citation statements)

References 69 publications

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“…Demyelination, a feature of several alphavirus infections in rodent models (del Canto and Rabinowitz, 1982;Suckling et al, 1978;Sheahan et al, 1983), has not been described in experimental flaviviral infections. One reported human SLE case had clinical features resembling cranial nerve root demyelination as seen in Guillain-Barre syndrome (Sanders et al, 1953), but this has not been a typical feature of human flaviviral infections.…”

Section: Pathological Changes In the Central Nervous Systemmentioning

confidence: 99%

Pathobiology of the Flaviviruses

Monath

1986

The Togaviridae and Flaviviridae

105

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Section: Pathological Changes In the Central Nervous Systemmentioning

confidence: 99%

Pathobiology of the Flaviviruses

Monath

1986

The Togaviridae and Flaviviridae

105

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“…Ethidium bromide (Yajima and Suzuki, 1979), lysolecithin (Hall, 1972), cuprizone (Blakemore, 1973;Hiremath et al, 1998), and viral infection in animal (Martin and Nathanson, 1979;Dal Canto and Rabinowitz, 1982;Stohlman and Hinton, 2001;Fazakerley and Walker, 2003) were extensively used. Other models, involving experimental allergic encephalomyelitis, have been widely produced (Swanborg, 1995;Bradl and Linington, 1996;Stefferl et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

Recovery of Myelin after Induction of Oligodendrocyte Cell Death in Postnatal Brain

Jalabi¹,

Boehm²,

Grucker³

et al. 2005

J. Neurosci.

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A transgenic mouse line (Oligo-TTK) was established to monitor oligodendrocyte cell death and myelin formation in the CNS. The expression of a conditionally toxic gene, the herpes simplex virus-1 thymidine kinase (HSV1-TK), was made under control of the MBP (myelin basic protein) gene promoter. A truncated form of the HSV1-TK (TTK) gene was used to avoid both bystander effect resulting from leaking in thymidine kinase activity and sterility in transgenic males observed in previous transgenic mice. The transgene was expressed in the CNS with a restricted localization in oligodendrocytes. Oligodendrocyte proliferation and myelin formation are therefore tightly controlled experimentally by administration of ganciclovir (GCV) via the induction of oligodendrocyte cell death. The most severe and irreversible hypomyelination was obtained when GCV was given daily from postnatal day 1 (P1) to P30. Oligodendrocyte plasticity and myelin recovery were analyzed in another phenotype generated by GCV treatment from P1 to P15. In this model, after dysmyelination, an apparent normal behavior was restored with no visible pathological symptoms by P30. Proliferating cells, which may be implicated in myelin repair in this model, are detected primarily in myelin tracts expressing the oligodendrocyte phenotype. Therefore, the endogenous potential of oligodendrocytes to remyelinate was clearly demonstrated in the mice of this study.

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“…Several experimental animal models have been developed in order to better understand the mechanism of demyelination. Experimental autoimmune encephalomyelitis and several virus-induced experimental models, including coronavirus infection in mice (5), have been instrumental in providing insight into the pathogenesis of demyelination.…”

mentioning

confidence: 99%

Demyelination Determinants Map to the Spike Glycoprotein Gene of Coronavirus Mouse Hepatitis Virus

Sarma¹,

Fu²,

Tsai

et al. 2000

J Virol

150

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Demyelination is the pathologic hallmark of the human immune-mediated neurologic disease multiple sclerosis, which may be triggered or exacerbated by viral infections. Several experimental animal models have been developed to study the mechanism of virus-induced demyelination, including coronavirus mouse hepatitis virus (MHV) infection in mice. The envelope spike (S) glycoprotein of MHV contains determinants of properties essential for virus-host interactions. However, the molecular determinants of MHV-induced demyelination are still unknown. To investigate the mechanism of MHV-induced demyelination, we examined whether the S gene of MHV contains determinants of demyelination and whether demyelination is linked to viral persistence. Using targeted RNA recombination, we replaced the S gene of a demyelinating virus (MHV-A59) with the S gene of a closely related, nondemyelinating virus (MHV-2). Recombinant viruses containing an S gene derived from MHV-2 in an MHV-A59 background (Penn98-1 and Penn98-2) exhibited a persistence-positive, demyelination-negative phenotype. Thus, determinants of demyelination map to the S gene of MHV. Furthermore, viral persistence is insufficient to induce demyelination, although it may be a prerequisite for the development of demyelination.Primary demyelination is a pathologic process in which myelin is destroyed, while neuronal axons remain relatively preserved. The demyelinating process can occur by either a direct attack on oligodendrocytes, the cells that produce and maintain myelin, or an autoimmune attack against myelin components, resulting in secondary destruction of oligodendrocytes. The most prevalent primary demyelinating disease in humans is multiple sclerosis (MS), which affects over a quarter of a million individuals in the United States (2). The etiology and pathogenesis of MS have long been investigated; however, causation has not been proven. There is a consensus that the process involves a T-cell-mediated autoimmune phenomenon that may be triggered by one or more viral infections (1). Several experimental animal models have been developed in order to better understand the mechanism of demyelination. Experimental autoimmune encephalomyelitis and several virus-induced experimental models, including coronavirus infection in mice (5), have been instrumental in providing insight into the pathogenesis of demyelination.Coronaviruses, members of the order Nidovirales, form a group of enveloped single-stranded RNA viruses (22,33,36,46). Many members of the nidoviruses, including coronaviruses and arteriviruses, infect the central nervous system and provide experimental animal model systems for neurologic diseases (30). The A59 and JHM strains of the murine member of the coronaviruses (mouse hepatitis virus [MHV]) produce demyelination in mice that mimics many of the pathologic features of MS (12,15,26,39,42,46,47). Chronic MHV-induced demyelination is immune mediated (11, 45), may be partially T-cell dependent (8), and is associated with viral persistence (25, 39) and concomit...

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Experimental models of virus‐induced demyelination of the central nervous system

Cited by 169 publications

References 69 publications

Pathobiology of the Flaviviruses

Pathobiology of the Flaviviruses

Recovery of Myelin after Induction of Oligodendrocyte Cell Death in Postnatal Brain

Demyelination Determinants Map to the Spike Glycoprotein Gene of Coronavirus Mouse Hepatitis Virus

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