DNA-BINDING-DEFECTIVE MUTANTS OF THE EPSTEIN-BARR-VIRUS LYTIC SWITCH ACTIVATOR ZTA TRANSACTIVATE WITH ALTERED SPECIFICITIES

The Epstein-Barr virus BRLF1 and BZLF1 genes are the first viral genes transcribed upon induction of the viral lytic cycle. The protein prod ucts of both genes (referred to here as Rta and Zta, respectively) act ivate expression of other viral genes, thereby initiating the lytic ca scade. Among the viral antigens expressed upon induction of the lytic cycle, however, Zta is unique in its ability to disrupt viral latency; expression of the BZLF1 gene is both necessary and sufficient for tri ggering the viral lytic cascade. We have previously shown that Zta can activate its own promoter (Zp), through binding to two Zta recognitio n sequences (ZIIIA and ZIIIB). Here we describe mutant Zta proteins th at do not bind DNA (referred to as Zta DNA-binding mutants Zdbm) but retain the ability to transactivate Zp. Consistent with the inability of these mutants to bind DNA, transactivation of Zp by Zdbm is not de pendent on the Zta recognition sequences. Instead, transactivation by Zdbm is dependent upon promoter elements that bind cellular factors. A n examination of other viral and cellular promoters identified promote rs that are weakly responsive or unresponsive to Zdbm. An analysis of a panel of artificial promoters containing one copy of various promote r elements demonstrated a specificity for Zdbm activation that is dist inct from that of Zta. These results suggest that non-DNA-binding form s of some transactivators retain the ability to transactivate specific target promoters without direct binding to DNA.