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- W2426993124 abstract "It has been well documented by several laboratories that adeno-associated virus (AAV) is able to inhibit HIV-1 replication and gene expression. This effect has been mapped to the AAV-encoded Rep78 protein. However, the mechanism by which Rep78 is able to inhibit HIV-1 is unclear. As Rep78 is a DNA binding transcription factor, the objective of this study was to investigate where Rep78 might bind within the HIV-1 long terminal repeat (LTR) sequences and to judge the importance of this protein-DNA interaction.Rep78's binding to HIV-LTR DNA was analyzed by electrophoretic mobility shift assay (EMSA). The importance of this protein-DNA interaction was analyzed using a Rep78 mutant defective for binding HIV-LTR DNA in an assay for monitoring gene expression (chloramphenicol acetyltransferase [CAT] assay).The preferred site for Rep78 binding was found to be adjacent to the HIV-LTR TATA box, within nt -54 to -34 relative to the site of transcription initiation. Furthermore, a Rep78 mutant with substitutions at amino acid residues 64 and 65 which was found defective for binding HIV-LTR DNA, was also found to be defective for inhibition of tat transactivated HIV-LTR gene expression.These data strongly suggest that Rep78's DNA binding ability is important for its mechanism of inhibition. Furthermore, the TATA box region of the HIV-LTR, to which Rep78 preferentially binds, is a likely target through which the inhibition takes place." @default.
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- W2426993124 date "1999-04-09" @default.
- W2426993124 modified "2023-10-16" @default.
- W2426993124 title "Involvement of protein-DNA interaction in adeno-associated virus Rep78-mediated inhibition of HIV-1." @default.
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