Inhibition of human immunodeficiency virus type 1 Tat activity by coexpression of heterologous trans activators.

AUTOR(ES)

Carroll, R

RESUMO

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).

Documentos Relacionados

• Activation of a heterologous promoter by human immunodeficiency virus type 1 Tat requires Sp1 and is distinct from the mode of activation by acidic transcriptional activators.
• Inhibition of Human Immunodeficiency Virus Type 1 Tat-trans-Activation-Responsive Region Interaction by an Antiviral Quinolone Derivative
• Inhibition of human immunodeficiency virus type 1 replication by a Tat-activated, transduced interferon gene: targeted expression to human immunodeficiency virus type 1-infected cells.
• Random mutagenesis of the human immunodeficiency virus type-1 trans-activator of transcription (HIV-1 Tat).
• Chemical synthesis of biologically active tat trans-activating protein of human immunodeficiency virus type 1.