Inhibition of human immunodeficiency virus type 1 Tat activity by coexpression of heterologous trans activators.
We examined the mechanism of Tat-mediated trans activation through competition experiments employing Tat proteins of human immunodeficiency virus type 1 (HIV-1) and equine infectious anemia virus (EIAV). EIAV Tat, as well as chimeric EIAV/HIV-1 Tat proteins, inhibited HIV-1 Tat-mediated trans activation in a cell-type-dependent fashion. Furthermore, these proteins inhibited trans activation by Tat-bacteriophage R17 coat protein chimeras. Inhibition resulted from competition between activation domains of effectors and competitors for a limiting cellular cofactor. The context in which competitor activation domains were expressed contributed to the extent of inhibition. In transfected cells, EIAV Tat and all chimeric competitors were located primarily in the cytoplasm, whereas HIV-1 Tat was primarily located in the nucleus. These data are consistent with a model for trans activation in which the activation domain of Tat associates with and conveys a cellular factor to the transcription complex via the trans-acting-responsive element (TAR).
Carroll
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R
Laboratory of Viral Carcinogenesis, National Cancer Institute, Frederick Cancer Research and Development Center, Maryland 21702-1201.
Peterlin
B M
BM
Derse
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D
D000595:Amino Acid Sequence; D001435:Bacteriophages / Q000235:genetics / Q000378:metabolism; D001667:Binding, Competitive; D003001:Cloning, Molecular; D015696:Gene Products, tat / Q000037:antagonists & inhibitors* / Q000235:genetics; D016325:HIV Long Terminal Repeat / Q000235:genetics*; D015497:HIV-1 / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D004860:Infectious Anemia Virus, Equine / Q000235:genetics; D008969:Molecular Sequence Data; D010957:Plasmids; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D054322:tat Gene Products, Human Immunodeficiency Virus
D015696:Gene Products, tat; D015534:Trans-Activators; D054322:tat Gene Products, Human Immunodeficiency Virus