Pathogenicity of Semliki Forest virus for the rat central nervous system and primary rat neural cell cultures: possible implications for the pathogenesis of multiple sclerosis

Abstract

The neurovirulent L10 strain of Semliki Forest virus (SFV) causes extensive neuronal damage in the central nervous system (CNS) of infected rats, and is probably the cause of death. The avirulent A7 and M9 strains do not cause extensive neuronal damage, but do induce immune-mediated CNS demyelination. In primary CNS cell cultures derived from rats, L10 multiplies more rapidly in neurons than avirulent strains, but infection with both virulent and avirulent strains causes depletion of oligodendrocytes from mixed glial cell cultures. It is proposed that the immune-mediated demyelination, which follows infection with avirulent strains, is induced by phagocytosis of myelin debris from infected oligodendrocytes, and the presentation of antigens derived from such debris to T-helper lymphocytes. Based on these and previous results, a scheme for the pathogenicity of defined strains of SFV is proposed. The applicability of this scheme to the understanding of human demyelinating disease such as multiple sclerosis is discussed.

Death mechanisms in cultured cells infected by Semliki Forest virus.

“…1 e). This confirms previous results for A7 and the virulent L10 strain of SFV (Atkins, 1983 ;Gates et al, 1985 ;Atkins et al, 1990).…”

“…It has previously been shown that infection of glial cell cultures with SFV results in depletion of the upper oligodendrocyte layer Gates et al, 1985 ;Atkins et al, 1990) and that this layer is selectively stained by anti-SFV antibody . SFV-infected oligodendrocytes can also be demonstrated in the animal (Atkins & Sheahan, 1982 ;Sheahan et al, 1983).…”

“…Fax j353 1 6799294. e-mail gatkins!tcd.ie Sheahan, 1982 ;Gates et al, 1985 ;Atkins et al, 1990 ;Smyth et al, 1990 ;Balluz et al, 1993 ;Fazakerley et al, 1993). Demyelination is triggered by infection of oligodendrocytes, which occurs in both the animal (Atkins & Sheahan, 1982 ;Sheahan et al, 1983) and in cultured glial cells Gates et al, 1985 ;Atkins et al, 1990).…”

“…Demyelination is triggered by infection of oligodendrocytes, which occurs in both the animal (Atkins & Sheahan, 1982 ;Sheahan et al, 1983) and in cultured glial cells Gates et al, 1985 ;Atkins et al, 1990).…”

“…Neuron and glial cell cultures were prepared from neonatal rat brain as previously described ( Gates et al, 1985 ;Atkins et al, 1990) ; neurons are 95 % pure and do not proliferate, whereas glial cells consist mainly of a mixture of proliferating oligodendrocytes and astrocytes (Walker et al, 1984). Elimination of proliferating glial cells in neuron cultures is accomplished by the addition of cytosine arabinoside (Natale et al, 1993).…”