TRANSCRIPTIONAL SILENCING OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 LONGTERMINAL 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-associ ated box (KRAB), present in the amino termini of a large number of Kru ppel-type zinc finger proteins is a strong repressor domain. In order to develop novel strategies to control human immunodeficiency virus ty pe 1 (HIV-1) gene expression, we constructed a series of expression ve ctors expressing the wild-type Tat or Tat transdominant negative mutan ts fused to the KRAB repressor domain. We found that the KRAB domain t ethered to the transactivating response element is able to suppress bo th basal and Tat-mediated activity of HIV-1 long terminal repeat-drive n gene expression. These results suggest that the KRAB repressor domai n fused to the Tat transdominant negative mutants can be successfully employed to control HIV-1 gene expression.