I George Miller MD
John F. Enders Professor of Pediatrics (Infectious Disease) and Professor of Epidemiology (Microbial Diseases) and of Molecular Biophysics and Biochemistry; Section Chief, Pediatric Infectious Diseases
Epstein-Barr Virus (EBV); Kaposi's Sarcoma-Associated Herpesvirus (KSHV); Tumor virology
Our research is directed at understanding a central unexplained phenomenon in virology, namely mechanisms underlying viral persistence and reactivation.
Extensive Research Description
We study two related human tumor viruses: Epstein-Barr virus (EBV), which is associated with lymphomas and carcinomas; and Kaposi’s sarcoma-associated herpesvirus (KSHV), which is associated with Kaposi’s sarcoma and lymphomas that occur in patients with AIDS. Both viruses establish “latent states” in host cells, during which only a limited number of viral genes are expressed. We have discovered multifunctional virally encoded transcription factors and replication proteins, ZEBRA and Rta in EBV and KSHV ORF50, which mediate a switch between latency and the lytic cycle. Our lab studies the control of ZEBRA, Rta and ORF50 expression and their mechanisms of action and interaction. We are interested in the basis of viral specificity of these activators. We also investigate how the immune system detects and regulates the latent and lytic cycle program of EBV in B cells.
- Chang, P.-J., Boonsiri, J., Wang, S.-S., Chen, L.-Y. and Miller, G. Binding of RBP-J Kappa (CSL) protein to the promoter of the Kaposi’s Sarcoma-associated herpesvirus ORF47 (gL) gene is a critical but not sufficient determinant of trans-activation by ORF50 protein. Virology 398:38-48, 2010. PMID 20006367.
- Daigle, D., Megyola, C., El-Guindy, A., Gradoville, G., Tuck, D., Miller, G. and Bhaduri-McIntosh, S. Up-regulation of STAT3 Marks Burkitt Lymphoma Cells Refractory to Epstein-Barr Virus Lytic Cycle Induction by HDAC Inhibitors. J. Virology 84:993-1004, 2010. PMID: 19889776
- Dela Cruz, C.S., S.R. Viswanathan, A.S. El-Guindy, D. Shedd and G. Miller. Complex N-linked Glycans on N89 of Kaposi’s Sarcoma Herpes virus-encoded Interleukin-6 mediate optimal function by affecting cytokine protein conformation. J. Biol. Chem. 284:29269-29282, 2009. PMID: 19690161
- Countryman, J., L. Gradoville, S. Bhaduri-McIntosh, J. Ye, L. Heston, S. Himmelfarb, D. Shedd and G. Miller. Stimulus Duration and Response Time Independently Influence the Kinetics of Lytic Cycle Reactivation of Epstein-Barr Virus. J. Virology 83:10694-709, 2009. PMID: 19656890
- Chen, L.-W., V. Raghavan, P.-J. Chang, D. Shedd, L. Heston, H.-J. Delecluse and G. Miller. Two Phenylalanines in the C-terminus of Epstein-Barr virus Rta protein reciprocally modulate its DNA binding and transactivation function. Virology 386:448-461, 2009. PMID: 19232420
- Park, R., L. Heston, D. Shedd, H.-J. Delecluse and G. Miller. Mutations of amino acids in the DNA recognition domain of Epstein Barr virus ZEBRA protein alter its sub-nuclear localization and affect formation of replication compartments. Virology 382:145-162, 2008. PMID: 18937960