Adoptive transfer of EAE-like lesions from rats with coronavirus-induced demyelinating encephalomyelitis

Abstract

Viruses have been found to induce inflammatory demyelinating lesions in central nervous system (CNS) tissue of both animal and man, either by natural infections or after vaccination. At least two different pathogenic mechanisms have been proposed for these changes, a cytopathic viral infection of oligodendroglia cells with subsequent cell death, and a host immune reaction against virus and brain antigens. We now report the occurrence of cell-mediated immune reactions against basic myelin proteins in the course of coronavirus infections in Lewis rats. Infection of rats with the murine coronavirus JHM leads to demyelinating encephalomyelitis developing several weeks to months postinfection. Lymphocytes from these diseased Lewis rats can be restimulated with basic myelin protein (BMP) and adoptive transfer of these cells leads to lesions resembling those of experimental allergic encephalomyelitis (EAE) in recipients, which can be accompanied by a mild clinical disease. This model demonstrates that a virus infection in CNS tissue is capable of initiating an autoimmune response which may be of pathogenic importance.

T cell memory specific for self and non-self antigens in rats persistently infected with Borna disease virus

“…Autoreactive T cells specific for MBP and PLP, the two major components of myelin proteins, were detected, although al a relatively low level compared wilh antiviral T cell reactivity. Such a myelin protein-directed self-reactivity of comparable magnitude has already been described in other models of virus-mediated encephalomyelitis in rats, e,g, in coronavirus- [7] and tneasles virus-induced encephalomyelitis [8], AutoreactiveTcellsshowedadefinite tendency to localize to the pt-LN and remain there for prolonged periods of time. The pl-LN are found in the thymic capsula in rats and in close proxitnity to the thymus on the capsula in mice [25].…”

“…e,g. coronavirus-induced encephalitis [7] or subacute measles encephalomyelitis [8]. BDV-infected animals were killed at day 25 after infection.…”

“…Examples comprise coronavirus-induccd cncephalomyelitis of Lewis rats [7]. characterized by marked demyelinating plaques and high titres of infectious virus, or measles-induced siibacute encephalotnyelitis in rats [8], where signs of detnyclination can hardly be observed.…”

No evidence for quasispecies populations during persistence of the coronavirus mouse hepatitis virus JHM: sequence conservation within the surface glycoprotein gene S in Lewis rats.

“…Many laboratories have used infection of rodents with murine coronavirus as an experimental model system for studying inflammatory demyelination and persistence in the central nervous system (CNS) (Kyuwa & Stohlman, 1990 ;Wege, 1995). Our interest in the pathogenicity of the neurotropic mouse hepatitis virus (MHV) JHM has centred on its ability to cause a subacute demyelinating encephalomyelitis (SDE) characterized by inflammation and selective loss of myelin in Lewis rats (Watanabe et al, 1983 ;Wege et al, 1984 b ;Zimprich et al, 1991 ;Barac-Latas et al, 1997).…”

“…Infection with a highly virulent MHV-JHM wild-type strain usually causes encephalomyelitis, independent of the age of the rat at time of infection (Watanabe et al, 1983 ;Zimprich et al, 1991 ;Wege, 1995 ;Barac-Latas et al, 1997). The variant MHV-JHM-Pi (Baybutt et al, 1984) replicates in the brain of adult Lewis rats without causing disease (Table 2).…”