Biophysics; Pediatrics; Sarcoma, Kaposi; Virology; Epstein-Barr Virus Infections; Infectious Disease Medicine
Molecular Virology: Virology laboratories
Our research is directed at understanding a central unexplained phenomenon in virology, namely mechanisms underlying viral persistence and reactivation.
Specialized Terms: Epstein-Barr Virus (EBV); Kaposi's Sarcoma-Associated Herpesvirus (KSHV); Tumor virology
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 PJ1, Boonsiri J, Wang SS, Chen LY, Miller G. Binding of RBP-Jkappa (CSL) protein to the promoter of the Kaposi's sarcoma-associated herpesvirus ORF47 (gL) gene is a critical but not sufficient determinant of transactivation by ORF50 protein. Virology. 2010 Mar 1;398(1):38-48.
- 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,
- Dela Cruz CS, Viswanathan SR, El-Guindy AS, Shedd D, Miller G. Complex N-linked glycans on Asn-89 of Kaposi sarcoma herpes virus-encoded interleukin-6 mediate optimal function by affecting cytokine protein conformation. J Biol Chem. 2009 Oct 23;284(43):29269-82
- Countryman J, Gradoville L, Bhaduri-McIntosh S, Ye J, Heston L, Himmelfarb S, Shedd D, Miller G. Stimulus duration and response time independently influence the kinetics of lytic cycle reactivation of Epstein-Barr virus. J Virol. 2009 Oct;83(20):10694-709
- Chen LW, Raghavan V, Chang PJ, Shedd D, Heston L, Delecluse HJ, Miller G. Two phenylalanines in the C-terminus of Epstein-Barr virus Rta protein reciprocally modulate its DNA binding and transactivation function. Virology. 2009 Apr 10;386(2):448-61
- Park R, Heston L, Shedd D, Delecluse HJ, Miller G. 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. 2008 Dec 20;382(2):145-62