Hl. Lipton et al., THE PREDOMINANT VIRUS-ANTIGEN BURDEN IS PRESENT IN MACROPHAGES IN THEILERS MURINE ENCEPHALOMYELITIS VIRUS-INDUCED DEMYELINATING DISEASE, Journal of virology, 69(4), 1995, pp. 2525-2533
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.