ASTROCYTE ACTIVATION BY SINDBIS VIRUS - EXPRESSION OF GFAP, CYTOKINES, AND ADHESION MOLECULES

Sindbis virus (SV) is a member of the alphaviruses which has served as a model system for studying viral encephalitis. Although astrocytes a re reported to be involved in the pathogenesis of various virus-relate d diseases, the effects of SV on astrocyte function have not been repo rted. In this study we compared the effects of two strains of SV, SVA, and SVNI, which differ in their neurovirulent properties, on astrocyt es with the use of cultured mouse astrocytes and the rat C6 glial cell line. We found that although both strains can similarly infect and re plicate in astrocytes, they induced different changes in the function of these cells. The neurovirulent strain, SVNI, induced a decrease in cell number and a marked increase in the expression of GFAP, whereas S VA did not alter these parameters. In addition, SVNI induced the secre tion of the cytokines TNF-alpha and IL-6, the expression of adhesion m olecules, and the production of the neurotrophic factor NGF. In contra st, SVA induced smaller increases in the secretion of IL-6 and NGF but did not alter the secretion of TNF-alpha and the expression of the ad hesion molecules. Neither virus induced the secretion of IL-2, IL-4, I L-10 and IFN-gamma or the expression of iNOS in the cells. These resul ts indicate that astrocytes, similar to neurons, can serve as target c ells to SV infection in the CNS. Moreover, the infection of astrocytes by SVNI leads to changes characteristic of reactive astrogliosis whic h may contribute to the pathogenesis of SV-induced encephalitis by enh ancing the local immune response in the CNS. (C) 1997 Wiley-Liss, Inc.