HIV-1 TAT ALTERS NORMAL ORGANIZATION OF NEURONS AND ASTROCYTES IN PRIMARY RODENT BRAIN-CELL CULTURES - RGD SEQUENCE DEPENDENCE

The HIV-1 trans-activator protein Tat has been implicated as a mediato r of neuronal dysfunction in several model systems. To explore the pos sibility that Tat can affect primary brain cells, we examined the effe ct of recombinant Tat protein on rat cortical brain cell cultures. Tat induced marked aggregation of neurons and astrocytes in developing cu ltures and caused the neuritic processes to coalesce into fascicles. C ell death was not seen and brain macrophages were not affected. These effects mapped to a different region from the trans-activation domain of Tat, as mutating the RGD (arginine-glycine-aspartic acid) sequence within the second exon abrogated aggregation and fascicle formation wi thout affecting trans-activation capacity. Such effects on primary neu rons and astrocytes may reflect specific interactions of Tat with unin fected cells within the CNS in vivo.