THE PREDOMINANT VIRUS-ANTIGEN BURDEN IS PRESENT IN MACROPHAGES IN THEILERS MURINE ENCEPHALOMYELITIS VIRUS-INDUCED DEMYELINATING DISEASE

Theiler's murine encephalomyelitis virus (TMEV) produces a persistent central nervous system infection and chronic, inflammatory demyelinati ng disease in susceptible mice. TMEV antigen(s) and RNA genome have be en detected in astrocytes, oligodendrocytes, and macrophages during pe rsistence. Whether there is a predominant cell type in which TMEV pers ists has not been resolved. Since TMEV-induced demyelinating lesions a re infiltrated with macrophages and a number of other persistent virus es show near-exclusive tropism for these phagocytic cells, we used two -color immunofluorescent staining with conventional and confocal micro scopy to colocalize TMEV to cells that stain with monoclonal antibodie s (MOMA-2 [unknown antigen], Mac-1 [CD11b], FA-11 [CD66], and 2F8 [sca venger receptor]) to macrophages in BeAn-infected SJL mice. A predomin ant virus antigen burden within macrophages infiltrating demyelinating lesions was seen. A dichotomy of cells staining for virus antigen(s) was found with infected cells containing either a large or small virus antigen load. Ninety percent of cells with a large virus antigen load were large phagocytes (20 to 50 mu m) that were readily detected at l ow power (5x objective). Cells with smaller amounts of virus antigen(s ) turned out to be either these same large phagocytic cells or much sm aller cells, congruent to 10 mu m in diameter. Forty percent of cells with a small virus antigen load were macrophages. The unidentified con gruent to 10-mu m cells that are virus antigen positive and macrophage negative in this study could still be macrophages, or they may be oli godendrocytes. The fact that virus was detected in the cytoplasm and n ot phagolysosomes of macrophages and the sheer mass of fluorescently s tained virus proteins in some macrophages suggest that TMEV persists i n these phagocytic cells by active virus replication.