While AIDS viral infection is known to severely depress immunological function, many patients also suffer from different neurological symptoms. The AIDS coat protein (gp120) appears to participate in both of these processes. The gp120 is part of a larger precursor (gp160) that is processed at a dibasic residue to yield gp120 and gp41. Since many neurons have enzymes that can process peptides at dibasic residues, these neurons should also be able to process gp160. My studies have been conducted with a neuronal cell line (GT1 cells) which biosynthesizes the peptide, luteinizing hormone-releasing hormone. I have found that these neurons express the genes for two different dibasic cleavage enzymes: furin and prohormone convertase (PC) 2. The gp160 can be processed to gp120 by these cells in vitro. Using antisense strate-gies, I have tried to eliminate or reduce the expression of furin or PC2. Reduction of furin expression is incompatible with survival of the cells. When PC2 expression is eliminated/depressed, gp160 processing is attenuated. Recently, I have found that the GT1 cells also express another processing enzyme, PC6. Presently, I am studying the contribution of the PC6 to gp160 processing and to determine whether regulation of PC2 or PC6 affects processing of gp160. Recently, my lab has begun investigating the possible signal transduction pathways of gp120 in the GT1 neurons. With Drs. Shears and Sumner, we have found that 24 hours incubation of 2.5 micrograms gp120 is not toxic to these neurons. The pg120 appears, however, to depress inositol phosphate metabolism. With Dr. David Armstrong, we have found that gp120 does not affect Ca2+ channels. We are presently conducting additional studies to determine whether other intracellular signaling pathways are affected by the gp120 in these cells.
