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 expression 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 phenotype and enhanced cell growth in soft agar. Further experiments using previously established nef-expressing human astrocytoma cell lines as well as nef-expressing murine fibroblasts suggested a brain cell-specific transforming activity of Nef. After implantation into syngeneic or nude mice both murine 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 neoplastic transformation of immortalized murine neural stem cells and enhances malignancy of low-tumorigenic human astrocytoma cells. Nef may therefore be involved in the development of AIDS-associated brain tumors.
Kramer-Hämmerle
S
S
Institute of Molecular Virology, GSF-National Research Center for Environment and Health, D-85764 Neuherberg, Germany.
Kohleisen
B
B
Hohenadl
C
C
Shumay
E
E
Becker
I
I
Erfle
V
V
Schmidt
J
J
D000818:Animals; D001254:Astrocytoma / Q000209:etiology / Q000473:pathology; D001932:Brain Neoplasms / Q000209:etiology / Q000473:pathology; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D002490:Central Nervous System / Q000166:cytology* / Q000473:pathology; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D015693:Gene Products, nef / Q000502:physiology*; D018014:Gene Transfer Techniques; D015754:Genes, nef; D015658:HIV Infections / Q000150:complications* / Q000235:genetics; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010641:Phenotype; D014407:Tumor Cells, Cultured; D054311:nef Gene Products, Human Immunodeficiency Virus
D015693:Gene Products, nef; D054311:nef Gene Products, Human Immunodeficiency Virus