HIV-GP120 AFFECTS THE FUNCTIONAL-ACTIVITY OF OLIGODENDROCYTES AND THEIR SUSCEPTIBILITY TO COMPLEMENT

The aim of this study was to assess whether the HIV protein gp120 can induce direct or/and indirect damage to oligodendrocytes (OL). Using h ighly purified cultures of rat OL, we report that gp120 binds to OL an d induces functional alterations in these cells. Indeed, the percentag e of cells expressing myelin basic protein (MBP) and the levels of all four MBP isoforms were substantially reduced after a 3-day treatment with 10 nM gp120. As gp120 depressed the ability of OL to reduce the t etrazolium salt MTT (a sign of mitochondrial impairment), the alterati on of MBP production may be a consequence of decreased metabolic activ ity. The above effects were accompanied by a small increase in the num ber of apoptotic nuclei (from 4.3% in controls to 17.6% in cells treat ed for 3 days with gp120). As complement can lyse OL and gp120 is know n to activate complement, we also studied the interaction between thes e two factors using OL cultures. The viral protein potentiated (by abo ut 25%) the lytic effect of complement, when administered to the cultu res 5 hr after complement, and depressed it (by about 30-40%), when ad ded 5 hr before complement. Heat denaturation and anti-gp120 antibodie s prevented the direct effect of gp120 on OL, but did not influence th e interactions between gp120 and complement. Some gp120 non glycosylat ed peptides (V3 loop, 254-274 and 415-435 peptides) mimicked the abili ty of gp120 to antagonize the lytic effect of complement, but not that of potentiating complement lytic activity. In conclusion, our study i ndicates that gp120 can alter OL functional activity directly and can interfere with OL susceptibility to complement mediated lysis. (C) 199 7 Wiley-Liss, Inc.