Macrophage infiltration, but not apoptosis, is correlated with immune-mediated demyelination following murine infection with a neurotropic coronavirus.
Mice infected with mouse hepatitis virus strain JHM (MHV-JHM) develop a chronic demyelinating encephalomyelitis that is in large part immune mediated. Potential mechanisms of immune activity were assessed using an adoptive transfer system. Mice deficient in recombinase-activating gene function (RAG1(-/-)), defective in B- and T-cell maturation, become persistently infected with MHV but do not develop demyelination. Adoptive transfer of splenocytes from mice immunized to MHV into RAG1(-/-) mice infected with an attenuated strain of the virus results in the rapid and progressive development of demyelination. Most striking, adoptive transfer resulted, within 5 to 6 days, in extensive recruitment of activated macrophages/microglia to sites of demyelination within the spinal cord. Clearance of virus antigen occurred preferentially from the gray matter of the spinal cord. Apoptotic cells were identified in both the gray and white matter of the central nervous system (CNS) from RAG1(-/-) mice before and after adoptive transfer, with a moderate increase in number, but not distribution, of apoptotic cells following the development of demyelination. These results suggest that apoptosis following MHV-JHM infection of the murine CNS is not sufficient to cause demyelination. These results, showing that macrophage recruitment and myelin destruction occur rapidly after immune reconstitution of RAG(-/-) mice, suggest that this will be a useful system for investigating MHV-induced demyelination.
Wu
G F
GF
Program in Neuroscience, University of Iowa, Iowa City, Iowa 52242, USA.
Perlman
S
S
D000818:Animals; D000956:Antigens, Viral / Q000276:immunology; D017209:Apoptosis; D002465:Cell Movement; D018352:Coronavirus Infections / Q000276:immunology* / Q000473:pathology*; D003711:Demyelinating Diseases / Q000276:immunology* / Q000821:virology*; D008262:Macrophage Activation / Q000276:immunology*; D051379:Mice; D006517:Murine hepatitis virus
D000956:Antigens, Viral