MYB PROTEIN BINDS TO HUMAN IMMUNODEFICIENCY VIRUS-1 LONG TERMINAL REPEAT (LTR) SEQUENCES AND TRANSACTIVATES LTR-MEDIATED TRANSCRIPTION

The protooncogene c-myb encodes a nuclear transcription factor that binds to DNA in a sequence-specific manner and transactivates transcription of several viral and cellular genes. The expression of c-myb is induced in mitogen-stimulated peripheral blood lymphocytes and is constitutively expressed in several CD4+ T-cell and myeloid cell lines, all of which constitute excellent targets for human immunodeficiency virus (HIV) infection and replication. We looked for the presence of Myb-binding motifs in human retroviral long terminal repeats (LTKs) and tested for Myb binding to HIV-1 LTR sequences by using a highly purified recombinant Myb protein. Our results show that HIV-1 LTR contains one high-affinity Myb-binding site along with two or more low-affinity binding sites. DNase I protection analysis as well as oligonucleotide competition experiments indicate that this binding is sequence specific. Introduction of purified Myb protein directly into HeLa cells harboring HIV-1 LTR chloramphenicol acetyltransferase vectors indicates that Myb protein transactivates HIV-1 LTR-mediated transcription. Thus, Myb protein binding to HIV LTR sequences may constitute one of the signals that regulates HIV-1 transcription.