Low Level of Lytic Replication in a Recombinant Epstein-Barr Virus Carrying an Origin of Replication Devoid of BZLF1-Binding Sites

Abstract

Binding of the BZLF1 viral transactivator to Epstein-Barr virus (EBV) oriLyt has been reported to be essential for viral DNA replication. We have constructed a recombinant virus (E2- oriLyt- R) in which the oriLyt BZLF1-binding sites (ZRE) were exchanged against papilloma E2-binding sites. A fusion protein between the BZLF1 protein-transactivating domain and the E2 protein-binding domain was able to reactivate lytic replication in E2- oriLyt- R. However, BZLF1 alone could also induce E2- oriLyt- R, albeit with much lower efficiency. ZRE are therefore important but not absolutely essential cis elements for lytic replication. This shows the importance of recombinants to evaluate viral functions.