SJL/J resistance to mouse hepatitis virus-JHM-induced neurologic disease can be partially overcome by viral variants of S and host immunosuppression.
The basis of the resistance of SJL/J mice to various strains of mouse hepatitis virus (MHV) has been the subject of some debate, especially as it relates to the number and nature of the determinants involved. Our previous work demonstrated that resistance by primary SJL/J glial cultures may involve events subsequent to viral gene expression, possibly due to a defect in cell-to-cell spread of the infection. Since S, the virion's major spike glycoprotein, is known to facilitate the spread of infection due to its syncytiogenic properties, we decided to investigate the role of this viral structural protein in resistance by primary SJL/J glial cells. Variants possessing deletions within the S coding region were able to grow in SJL/J glial cells 10-100 times easier and fuse five-times more efficiently than wt virus. Induction of neurologic disease in SJL/J mice following intracranial inoculation with either wt JHMV or the S deletion variant, AT11f cord, was age-dependent, occurring only in animals inoculated under 4 weeks of age. Resistance in older animals to wt and variant viruses could be abrogated by immunosuppression with cyclosporin A. However, both disease incidence and viral brain titers were higher in animals receiving the JHM variant AT11f cord virus, suggesting that SJL/J resistance to neurologic disease may manifest itself through interactions between inefficient cell-to-cell spread of the infection and protective aspects of the immune response.
Pasick
J M
JM
Department of Microbiology and Immunology, University of Western Ontario, London, Canada.
Wilson
G A
GA
Morris
V L
VL
Dales
S
S
D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D002493:Central Nervous System Diseases / Q000235:genetics / Q000276:immunology* / Q000382:microbiology*; D004198:Disease Susceptibility; D014644:Genetic Variation; D006524:Hepatitis, Viral, Animal / Q000235:genetics* / Q000276:immunology*; D007113:Immunity, Innate / Q000187:drug effects; D007165:Immunosuppression Therapy; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D006517:Murine hepatitis virus / Q000235:genetics / Q000276:immunology*; D009457:Neuroglia / Q000382:microbiology; D017384:Sequence Deletion; D013116:Spinal Cord / Q000382:microbiology; D015678:Viral Structural Proteins / Q000235:genetics; D014779:Virus Replication
D015678:Viral Structural Proteins