ACTIVATION OF ASTROCYTES IN THE SPINAL-CORD OF MICE CHRONICALLY INFECTED WITH A NEUROTROPIC CORONAVIRUS

Mice infected with the neurotropic JHM strain of mouse hepatitis virus (MHV-JHM) develop a demyelinating encephalomyelitis several weeks aft er infection. Astrogliosis and infiltration of inflammatory cells are prominent findings in the brains and spinal cords of infected mice. In this report, astrocytes in infected spinal cords were analyzed for ex pression of three pleiotropic cytokines, TNF-alpha, IL-1 beta, and IL- 6; Type 2 nitric oxide synthase (iNOS); and MHC class I and II antigen . The data show that all three cytokines and iNOS are expressed by ast rocytes in chronically infected spinal cords. These activated astrocyt es are localized to areas of virus infection and demyelination, althou gh most of the astrocytes expressing these proteins are not MHV-infect ed. MHC class I and II antigen can be detected in these spinal cords a s well, but not in cells with the typical morphology of astrocytes. TN F-alpha, IL-6, and iNOS are also evident in the brains of mice with MH V-induced acute encephalitis, but in marked contrast to the results ob tained with the chronically infected mice, most of the cells expressin g these cytokines or iNOS had the morphology of macrophages or other m ononuclear cells and very few appeared to be astrocytes. Additionally, astrocytes and, most likely, oligodendrocytes are infected in the spi nal cords of mice with chronic demyelination. These results are consis tent with a role for both viral infection of glial cells and high loca lized revels of proinflammatory cytokines and nitric oxide in the demy elinating process in mice infected with MHV-JHM. They also show that a nalogously to the human demyelinating disease, multiple sclerosis, ast rocytes are a major cellular source for these cytokines in mice with c hronic, but not acute disease. (C) 1995 Academic Press, Inc.