HIV type 1 Nef promotes neoplastic transformation of immortalized neural cells

To study the effects of HIV-1 Nef on CNS-derived cells in vivo, an expressi on system based on the murine neural stem cell line C17.2 was established. Stable expression of LAV-1(Bru)-nef in these cells induced a transformed ph enotype and enhanced cell growth in soft agar, Further experiments using pr eviously established nef-expressing human astrocytoma cell lines as well as nef-expressing murine fibroblasts suggested a brain cell-specific transfor ming activity of Nef. After implantation into syngeneic or nude mice both m urine and human nef-expressing CNS-derived cells induced tumor development. Interestingly, human astrocytoma cells expressing a Nef mutant carrying a disrupted SH3-binding motif involved in protein-protein interactions failed to induce tumor formation. These in vivo data suggest that Nef promotes ne oplastic transformation of immortalized murine neural stem cells and enhanc es malignancy of low-tumorigenic human astrocytoma cells, Nef may therefore be involved in the development of AIDS-associated brain tumors.