DNA Replication; Oncogenic Viruses; Pediatrics; Phosphorylation; Transcription Factors; Tumor Virus Infections; Epstein-Barr Virus Infections; Infectious Disease Medicine
Discovery to Cure Internship
Our research focuses on the process of Epstein-Barr virus (EBV) lytic DNA replication. Epstein-Barr virus, an oncogenic virus, is associated with lymphomas and carcinomas, such as Burkitt lymphoma and nasopharyngeal carcinoma. The EBV life cycle is divided into two phases, latent and lytic. EBV is predominantly latent. The only route for the virus to amplify and infect new individuals is through activation of its lytic gene expression program. ZEBRA, a viral transcription activator, mediates the switch from the latent to the lytic phase. ZEBRA is also essential for the process of viral DNA replication; it binds to the origin of lytic replication and recruits other components of the replication machinery. In our studies we found that phosphorylation of the EBV ZEBRA protein regulates its capacity to interact with the origin of replication. These studies led us to characterize a novel role for replication proteins in the process of origin recognition. In addition, we have developed various genetic approaches to assess the involvement of other lytic cycleproteins in the process of viral DNA replication. For example, we have recently found that the EBV Rta protein, which serves as a transcription factor, plays an independent role in replicating the endogenous viral genome. Our goal is to delineate the viral and cellular proteins involved in the process of lytic DNA replication and their role in replication. Identifying the major players responsible for viral DNA replication has a strong potential to generate new strategies for the development of antiviral drugs against EBV.
Specialized Terms: DNA replication; Tumor virus; Herpesvirus; Oncogenic; Transcription factor; Replication protein; Phosphorylation; Protein modification; Kinase
Phosphoacceptor site S173 in the regulatory domain of Epstein-Barr Virus ZEBRA protein is required for lytic DNA replication but not for activation of viral early genes.
El-Guindy, A., Heston, L., Delecluse, H.-J., and Miller, G. (2007) Phosphoacceptor site S173 in the regulatory domain of Epstein-Barr Virus ZEBRA protein is required for lytic DNA replication but not for activation of viral early genes.
A subset of replication proteins enhances origin recognition and lytic replication by the Epstein-Barr virus ZEBRA protein
El-Guindy A, Heston L, Miller G (2010) A subset of replication proteins enhances origin recognition and lytic replication by the Epstein-Barr virus ZEBRA protein. PLoS Pathog 6(8):e1001054 PMID 20808903