Virulent and avirulent strains of Semliki Forest virus show similar cell tropism for the murine central nervous system but differ in the severity and rate of induction of cytolytic damage

Abstract

The pathogenicity of the avirulent, demyelinating A7 strain of Semliki Forest virus (SFV) and the virulent SFV4 strain (derived from an infectious clone) for the central nervous system of adult BALB/c mice following intranasal infection was compared. The techniques used included immunocytochemistry using anti-SFV antibody and antibodies to cell markers, in situ hybridization (ISH) using a biotinylated cDNA probe specific for SFV, and immunocytochemistry/ISH double labelling. Whereas SFV4 was lethal at 4 days post-infection, A7-infected mice appeared normal at all times. Neuronal necrosis in the pyriform cortex was present in both infections, but developed sooner and was more severe following infection with SFV4 than with A7. Intact neurons and putative oligodendrocytes contained viral RNA and virus-specific antigen in SFV4 infected mice; viral RNA but not virus-specific antigen was detected in similar cells in A7-infected mice. These results confirm that SFV4 and A7 share similar cell tropisms for the murine central nervous system, but differ in the severity and rate of development of cytolytic damage. Intranasal infection is an efficient monitoring system for studies of the molecular basis of pathogenicity of SFV infection in mice.

Mechanisms of Immunopathology in Murine Models of Central Nervous System Demyelinating Disease

“…SFV is a neuroinvasive and neurotropic virus that infects CNS neurons and oligodendrocytes (74,75). In adult C57BL/6 and BALB/c mice, the virus is for the most part cleared from the CNS by day 6 postinfection.…”

Altered IL‐1β and IL‐2 mRNA Expression in Murine Splenic Cells After Concomitant Stimulation by Semliki Forest Virus and Lipopolysaccharide

“…However, infection with the avirulent variant strain (SFV-A7) is asymptomatic [9][10][11][12][13]. In a previous study, we observed an abortive infection of SFV-A7 on mouse splenic cells cultured in vitro [4]: viral protein was detected but no infectious virus released.…”

Sequence analysis of the avirulent, demyelinating A7 strain of Semliki Forest virus.

“…or intraperitoneally (i.p. ; Balluz et al, 1993). To verify infection, all surviving mice were challenged with a normally lethal dose of 10' p.f.u.…”

“…Growth and assay of the avirulent A7 strain of SFV in BHK-21 cells was as previously described (Balluz et al, 1993). The virulent SFV4 strain of SFV was produced by transcription and electroporation of the pSP6-SFV4 infectious clone of SFV (Glasgow et al, 1991).…”

“…Virulent strains such as the prototype strain or the L10 strain cause a lethal threshold of damage to neurons in the CNS (Atkins & Sheahan, 1982 ;Atkins et al, 1990 ;Smyth et al, 1990 ;Glasgow et al, 1991 ;Balluz et al, 1993). Avirulent strains or mutants such as A7 and M9 are less cytopathic for neurons (Atkins et al, 1985(Atkins et al, , 1995Fazakerley et al, 1993) and induce demyelination which is triggered by infection of oligodendrocytes (Atkins et al, 1985(Atkins et al, , 1994 and is partially immune-mediated (Gates et al, 1984 ;Fazakerley & Webb, 1987 ;Subak-Sharpe et al, 1993).…”