Coronavirus-induced encephalomyelitis: balance between protection and immune pathology depends on the immunization schedule with spike protein S.
The neurotropic mouse hepatitis virus MHV-JHM induces central nervous system (CNS) demyelination in Lewis rats that pathologically resembles CNS lesions in multiple sclerosis. The mechanisms of MHV-JHM-induced demyelination remain unclear and several studies have implicated the role of the immune response in this process. We have shown previously that protective immunity against MHV-JHM-induced encephalomyelitis was induced by immunization with a vaccinia virus (VV) recombinant expressing MHV-JHM S-protein (VV-S). Here, we present evidence that the time of MHV-JHM challenge after immunization with VV-S plays a critical role in protective immunity. The induction of virus-neutralizing S-protein-specific antibodies prior to the MHV-JHM challenge modulates the disease process and a subacute encephalomyelitis based on a persistent virus infection developed. Typical pathological alterations were lesions of inflammatory demyelination. In addition, the results indicate that after seroconversion, CD8+ T cells were no longer essential for virus elimination in contrast to their role in protection during acute encephalomyelitis.
Flory
E
E
Institute of Virology and Immunobiology, University of Würzburg, Germany.
Stühler
A
A
Barac-Latas
V
V
Lassmann
H
H
Wege
H
H
D000818:Animals; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D000956:Antigens, Viral / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D018352:Coronavirus Infections / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D003711:Demyelinating Diseases / Q000276:immunology; D004679:Encephalomyelitis / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D005260:Female; D007114:Immunization; D007074:Immunoglobulin G / Q000097:blood; D008212:Lymphocyte Depletion; D008562:Membrane Glycoproteins / Q000276:immunology*; D051379:Mice; D006517:Murine hepatitis virus / Q000276:immunology* / Q000302:isolation & purification; D051381:Rats; D011917:Rats, Inbred Lew; D011993:Recombinant Fusion Proteins / Q000276:immunology; D064370:Spike Glycoprotein, Coronavirus; D013997:Time Factors; D014759:Viral Envelope Proteins / Q000276:immunology*; D014765:Viral Vaccines / Q000276:immunology*
D000914:Antibodies, Viral; D000956:Antigens, Viral; D007074:Immunoglobulin G; D008562:Membrane Glycoproteins; D011993:Recombinant Fusion Proteins; D064370:Spike Glycoprotein, Coronavirus; D014759:Viral Envelope Proteins; D014765:Viral Vaccines; C578557:spike glycoprotein, SARS-CoV; C578553:spike protein, mouse hepatitis virus