Coronavirus-induced demyelination occurs in the presence of virus-specific cytotoxic T cells.
C57BI/6, but not BALB/c, mice infected with mouse hepatitis virus strain JHM (MHV-JHM) develop a late onset, symptomatic demyelinating encephalomyelitis. In this report, we characterized anti-viral cytotoxic T cells in the central nervous system and spleen during the acute and chronic stages of the MHV infection. The data show that C57BI/6 mice display a cytotoxic T cell (CTL) response to the surface (S) glycoprotein and this response can be demonstrated in lymphocytes isolated from the brains and spinal cords of mice both acutely and persistently infected with MHV-JHM. Thus, the anti-S CTL activity present in the central nervous system of chronically infected animals is not sufficient to prevent the demyelinating process. BALB/c mice have been shown previously to mount a CTL response against the nucleocapsid (N) protein (Stohlman et al., 1992). Since C57BI/6 mice do not mount a response to the N protein, the role of the N-specific response in preventing the late onset disease was assessed using B10.A(18R) mice, recombinant in the H-2 locus. These mice contain the d alleles of the D and L loci and exhibit a CTL response against the N protein. However, unlike the BALB/c mice, these animals develop the late onset symptomatic disease. These results suggest that the N-specific response is partially protective against the development of the demyelinating disease, but that additional factors are also likely to be involved.
Castro
R F
RF
Department of Microbiology, University of Iowa, Iowa City 52242.
Evans
G D
GD
Jaszewski
A
A
Perlman
S
S
D000208:Acute Disease; D000818:Animals; D016827:CD8 Antigens / Q000276:immunology; D002213:Capsid / Q000276:immunology; D002490:Central Nervous System / Q000166:cytology / Q000276:immunology / Q000473:pathology; D002908:Chronic Disease; D018352:Coronavirus Infections / Q000276:immunology*; D003711:Demyelinating Diseases / Q000276:immunology*; D004679:Encephalomyelitis / Q000276:immunology*; D006183:H-2 Antigens / Q000235:genetics; D008562:Membrane Glycoproteins; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D006517:Murine hepatitis virus / Q000276:immunology*; D013045:Species Specificity; D064370:Spike Glycoprotein, Coronavirus; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic; D014758:Viral Core Proteins / Q000276:immunology; D014759:Viral Envelope Proteins / Q000276:immunology
D016827:CD8 Antigens; D006183:H-2 Antigens; D008562:Membrane Glycoproteins; D064370:Spike Glycoprotein, Coronavirus; D014758:Viral Core Proteins; D014759:Viral Envelope Proteins