Myb protein binds to human immunodeficiency virus 1 long terminal repeat (LTR) sequences and transactivates

P Dasgupta1, P Saikumar, C D Reddy

  • 1Wistar Institute of Anatomy and Biology, Philadelphia, PA 19104.

Insights

The protooncogene c-myb binds to human immunodeficiency virus (HIV) long terminal repeats (LTRs), regulating viral transcription. This Myb protein binding to HIV-1 LTR sequences is sequence-specific and transactivates viral gene expression.

Area of Science:

  • Molecular Biology
  • Virology
  • Oncology

Background:

  • The protooncogene c-myb encodes a nuclear transcription factor involved in gene regulation.
  • c-myb expression is induced in lymphocytes and constitutively present in CD4+ T-cells and myeloid cells, which are targets for HIV.
  • Understanding factors regulating HIV transcription is crucial for therapeutic development.

Purpose of the Study:

  • To investigate the presence and function of Myb-binding motifs in human immunodeficiency virus (HIV) long terminal repeats (LTRs).
  • To determine if Myb protein can bind to and influence HIV-1 LTR-mediated transcription.

Main Methods:

  • Bioinformatic analysis to identify Myb-binding motifs in retroviral LTRs.
  • Electrophoretic mobility shift assays (EMSA) and DNase I protection assays using recombinant Myb protein and HIV-1 LTR sequences.
  • Reporter gene assays (chloramphenicol acetyltransferase) in HeLa cells to assess Myb's effect on HIV-1 LTR transcription.

Main Results:

  • HIV-1 LTR contains one high-affinity and multiple low-affinity Myb-binding sites.
  • Myb protein binds to HIV-1 LTR sequences in a sequence-specific manner.
  • Myb protein transactivates transcription mediated by the HIV-1 LTR.

Conclusions:

  • Myb protein can bind to specific sites within the HIV-1 LTR.
  • Myb protein acts as a transactivator of HIV-1 LTR transcription.
  • Myb protein binding to HIV LTR sequences is a potential regulatory mechanism for HIV-1 transcription.

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