Schematic representation of the tet-Off system. The tTA binds specifically to the tet-Off (tetO) operator sequences upstream of the CMV promoter (P_CMV). The tetO/P_CMV represents the tetracycline response element (TRE). In the presence of tetracycline, the binding of this antibiotic to tTA blocks its binding to the TRE (left), and transactivation of the LMP1 oncogene does not occur. The LMP1 oncogene, under the control of TRE, is activated by tTA (right) in the absence of tetracycline resulting in LMP1 oncoprotein expression. tetR, tetracycline repressor protein; VP16, herpes-simplex virus encoded transcriptional activator.