A. Menard et al., A CYTOTOXIC FACTOR FOR GLIAL-CELLS - A NEW AVENUE OF RESEARCH FOR MULTIPLE-SCLEROSIS, Cellular and molecular biology, 43(6), 1997, pp. 889-901
A novel retrovirus, provisionally called Multiple Sclerosis RetroVirus
(MSRV), was recently described in multiple sclerosis (MS). We report
here that monocyte/macrophage culture supernatants from MS patients co
ntaining reverse transcriptase activity secrete a cytotoxin which indu
ces death of primary mouse cortical glial cells. This cytotoxin, which
was also found in MS cerebrospinal fluid, specifically causes death o
f mouse immortalized astrocytes and oligodendrocytes in vitro and seem
s to be associated to MSRV-specific RNA. This toxic factor, called gli
otoxin, is present only in active cases of MS and is a stable glycosyl
ated protein of 17 kDa, in CSF as well as in monocyte/macrophage cultu
re supernatants. Since this gliotoxin is highly toxic for glial cells,
it may represent an initial pathogenic factor, leading to the neuropa
thological features of MS, like blood brain barrier disruption and dem
yelination.