Transiently transfected and stably integrated HIV-1 LTR responds differentially to the silencing activity of the Kruppel-associated box (KRAB) transcriptional repressor domain

It has been demonstrated previously that the transcriptional repressor doma in called the Kruppel-associated box (KRAB), conserved in a large number of Kruppel-type zinc finger proteins, fused to Tat transdominant negative mut ants, is able to silence HIV-1 long terminal repeat (LTR)-driven gene expre ssion in transient transfection assays. In the present study chimeric Tat m utant-KRAB retroviral expression vectors were used to control HIV-1 replica tion in acutely infected cells. It was found that while transient and stabl e expression of Tat mutant-KRAB chimeric proteins represses HIV-1 LTR-drive n gene transcription in transient assays, stable expression of Tat mutant-K RAB chimeric molecules does not confer resistance to HIV-1 infection in Jur kat T lymphocytic cell lines. The results provide further evidence that tra nsient transfection may underestimate the role of chromosomal structure in transcriptional regulation and highlight the caveat of direct extrapolation of transient results for designing gene therapy strategies for efficient c ontrol of HIV-1 infection. (C) 1999 Wiley-Liss, Inc.