TRANSCRIPTIONAL SILENCING OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 LONG TERMINAL REPEAT-DRIVEN GENE-EXPRESSION BY THE KRUPPEL-ASSOCIATED BOX REPRESSOR DOMAIN TARGETED TO THE TRANSACTIVATING RESPONSE ELEMENT

The evolutionarily conserved protein domain, called the Kruppel-associated box (KRAB), present in the amino termini of a large number of Kruppel-type zinc finger proteins is a strong repressor domain. In order to develop novel strategies to control human immunodeficiency virus type 1 (HIV-1) gene expression, we constructed a series of expression vectors expressing the wild-type Tat or Tat transdominant negative mutants fused to the KRAB repressor domain. We found that the KRAB domain tethered to the transactivating response element is able to suppress both basal and Tat-mediated activity of HIV-1 long terminal repeat-driven gene expression. These results suggest that the KRAB repressor domain fused to the Tat transdominant negative mutants can be successfully employed to control HIV-1 gene expression.