title: Upstream stimulating factor affects human immunodeficiency virus type 1 (HIV-1) long terminal repeat-directed transcription in a cell-specific manner, independently of the HIV-1 subtype and the core-negative regulatory element.
abstract: Human immunodeficiency virus type 1 (HIV-1) is classified into subtypes on the basis of phylogenetic analysis of sequence differences. Inter- and intra-subtype polymorphism extends throughout the genome, including the long terminal repeat (LTR). In this study, the importance of the upstream stimulating factor (USF)-binding site (E-box) in the core-negative regulatory element (NRE) of the LTR of HIV-1 subtypes A, B, C, D, E and G was investigated. In vivo, USF was found to repress transcription directed from representative HIV-1 LTR sequences of all the subtypes tested in an epithelial cell line, yet activate the same transcription in a T-cell line. Mutation of the core-NRE USF site of the representative subtype B LTR did not affect the cell-specific, subtype-independent, dual role of USF. In vitro binding assays showed that recombinant USF(43) interacts with the core-NRE from subtypes B and C, but not A, D, E or G. Thus, USF affects LTR-directed transcription in a cell-specific manner, independently of both the HIV-1 subtype from which the LTR was derived and the core-NRE USF site sequences.
authors.affiliation: Division of Clinical Virology, Karolinska Institute, F68, Huddinge University Hospital, S-141 86 Huddinge, Stockholm, Sweden1.
authors.forename: Mojgan H
authors.initials: MH
authors.lastname: Naghavi
authors.affiliation: Laboratory of Biochemistry and Molecular Biology, The Rockefeller University, 1230 York Avenue, New York 10021-6399, USA3.
authors.forename: Mario C
authors.initials: MC
authors.lastname: Estable
authors.affiliation: Department of Medical Biochemistry and Microbiology, BMC, Uppsala University, S-751 23 Uppsala, Sweden2.|Division of Clinical Virology, Karolinska Institute, F68, Huddinge University Hospital, S-141 86 Huddinge, Stockholm, Sweden1.
authors.forename: Stefan
authors.initials: S
authors.lastname: Schwartz
authors.affiliation: Laboratory of Biochemistry and Molecular Biology, The Rockefeller University, 1230 York Avenue, New York 10021-6399, USA3.
authors.forename: Robert G
authors.initials: RG
authors.lastname: Roeder
authors.affiliation: Division of Clinical Virology, Karolinska Institute, F68, Huddinge University Hospital, S-141 86 Huddinge, Stockholm, Sweden1.
authors.forename: Anders
authors.initials: A
authors.lastname: Vahlne
mesh_terms: D000818:Animals; D001665:Binding Sites; D004268:DNA-Binding Proteins; D015967:Gene Expression Regulation, Viral; D016325:HIV Long Terminal Repeat / Q000235:genetics*; D015497:HIV-1 / Q000235:genetics*; D006367:HeLa Cells; D006801:Humans; D019169:Jurkat Cells; D051381:Rats; D012045:Regulatory Sequences, Nucleic Acid; D014157:Transcription Factors / Q000378:metabolism*; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured; D051720:Upstream Stimulatory Factors
chemical_list: D004268:DNA-Binding Proteins; D014157:Transcription Factors; C497181:USF1 protein, human; D051720:Upstream Stimulatory Factors; C497182:Usf1 protein, rat