Differential transcriptional regulation by human immunodeficiency virus type 1 and gp120 in human astrocytes.
Astrocytes may be infected with the human immunodeficiency virus type 1 (HIV-1) or exposed to the HIV protein gp120, yet their role in the pathogenesis of HIV dementia is largely unknown. To characterize the effects of HIV on astrocytic transcription, microarray analysis and ribonuclease protection assays (RPA) were performed. Infection of astrocytes by HIV or treatment with gp120 had differential and profound effects on gene transcription. Of the 1153 oligonucleotides on the immune-based array, the expression of 108 genes (53 up; 55 down) and 82 genes (32 up; 50 down) were significantly modulated by gp120 and HIV infection respectively. Of the 1153 oligonucleotides on the neuro-based array, 58 genes (25 up; 33 down) and 47 genes (17 up; 30 down) were significantly modulated by gp120 and HIV infection respectively. Chemokine and cytokine induction occurred predominantly by HIV infection, whereas gp120 had no significant effect. These results were confirmed by RPA. The authors conclude that profound alterations of astrocytic function occur in response to HIV infection or interaction with viral proteins, suggesting that astrocytes may play an important role in the pathogenesis of HIV dementia.
Galey
D
D
Department of Neurology, Johns Hopkins School of Medicine, Baltimore, Maryland 21287, USA.
Becker
K
K
Haughey
N
N
Kalehua
A
A
Taub
D
D
Woodward
J
J
Mattson
M P
MP
Nath
A
A
D015526:AIDS Dementia Complex / Q000235:genetics / Q000378:metabolism / Q000821:virology; D001253:Astrocytes / Q000378:metabolism / Q000821:virology*; D015152:Blotting, Northern; D001921:Brain / Q000166:cytology / Q000196:embryology; D002478:Cells, Cultured / Q000378:metabolism / Q000821:virology; D018925:Chemokines / Q000096:biosynthesis / Q000235:genetics; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D020869:Gene Expression Profiling; D015967:Gene Expression Regulation, Viral; D015699:HIV Envelope Protein gp120 / Q000494:pharmacology*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012260:Ribonucleases / Q000378:metabolism; D014158:Transcription, Genetic
D018925:Chemokines; D016207:Cytokines; D018076:DNA, Complementary; D015699:HIV Envelope Protein gp120; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D012260:Ribonucleases