Interactions of the transcription factor AP-1 with the long terminal repeat of different human immunodeficiency virus type 1 strains in Jurkat, glial, and neuronal cells.
Human immunodeficiency virus type 1 (HIV-1) infection of the neuronal and astroglial cells of the central nervous system has been proposed to contribute to HIV-1-associated dementia. Recently it was shown that differences in the nucleotide sequence of the long terminal repeat (LTR) of different HIV-1 strains govern the tissue-specific pattern of viral expression. The LTR from central nervous system-derived HIV-1 strains JR-FL and JR-CSF directs expression in the neurons of transgenic mice, in contrast with the lymphotropic LAI strain. By in vitro footprinting, gel retardation, and methylation interference experiments, we have studied the interactions of host cell proteins from human neuronal, glial, HeLa, and Jurkat T cells with the LTRs from the neurotropic JR-FL and JR-CSF strains, compared with the LAI strain. Proteins belonging to the nuclear receptor family bind with different affinities to variant -352 to -324 sites. Gel supershift assays with Jun and Fos antibodies showed that the AP-1 transcription factor present in the various cell types was unable to recognize the -352 to -324 and -306 to -285 AP-1 putative binding sites. Interestingly, Jun and Fos components of AP-1 interact with the variant TGGCTCA sequence located in the -247 to -222 region of both neurotropic strains. These interactions were cell type specific, since they were detected only with extracts from glial and HeLa cells and not from neuronal or Jurkat cells. Cotransfection experiments further revealed that the -247 to -222 sequence is able to mediate AP-1-induced transcriptional activation in glial and not neuronal cells.
D000818:Animals; D001254:Astrocytoma; D001483:Base Sequence; D001665:Binding Sites; D001667:Binding, Competitive; D002460:Cell Line; D004279:DNA, Viral / Q000378:metabolism*; D014644:Genetic Variation; D016325:HIV Long Terminal Repeat; D015497:HIV-1 / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008745:Methylation; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009447:Neuroblastoma; D009457:Neuroglia / Q000378:metabolism* / Q000821:virology; D009474:Neurons / Q000378:metabolism* / Q000821:virology; D009687:Nuclear Proteins / Q000302:isolation & purification / Q000378:metabolism*; D009838:Oligodeoxyribonucleotides; D013379:Substrate Specificity; D018808:Transcription Factor AP-1 / Q000302:isolation & purification / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D004279:DNA, Viral; D009687:Nuclear Proteins; D009838:Oligodeoxyribonucleotides; D018808:Transcription Factor AP-1