Human viruses are responsible for about 20% of human malignancies worldwide and offer unique opportunities for early diagnosis, prevention, and therapeutic intervention. Our experiments began with the study of the fundamental mechanisms by which Epstein-Barr Virus (EPV), an important causative agent of lymphomas, Hodgkin's Disease and Naso-pharyngeal carcinoma, uniquely and efficiently causes the uncontrolled proliferation and survival of normal human B lymphocytes. We have discovered that the virus uses only five genes to cause B cell proliferation. These genes encode nuclear proteins that usurp control over Notch regulated cell promoters, including the c-myc promoter, and an integral membrane protein that constitutively activates CD40 signaling pathways. We are currently investigating the genetics and biochemistry of the molecular and sub-molecular processes through which the viral proteins effect changes in cell signal transduction, transcription, growth, and survival so as to validate targets that can be used in assays to identify chemical inhibitors.

EBV is unique among human viruses in inducing continuous proliferation of B lymphocytes, the important host cell for EBV latency. In B lymphocytes, EBV encodes nuclear antigen (EBNA) and integral membrane (LMP) proteins, which induce cell cycle transit and lymphoblast proliferation. In humans with normal T cell function, immune T lymphocytes emerge in response to peptides from the EBNAs and LMPs, which are presented in the context of Class I and II MHC molecules on cell surfaces. Immune T cells kill and enforce tight control of EBV infected lymphocytes.

Ongoing projects in our lab involve: (1) Elucidation of the molecular and sub-molecular pathways by which Notch and viral proteins regulate the c-myc promoter. Structural studies of a key viral and cellular interaction site. (2) Elucidation of the molecular and sub-molecular pathways by which CD40 and a viral protein co-stimulate cell growth and survival. (3) Proteinomic and cell genetic screens for novel genes in the CD40 and viral protein NF-kB, Junk, and p38 pathways. (4) Sub-molecular mechanisms by which a viral protein permits episome replication and maintenance.

Elliott Kieff was born in Philadelphia and educated in public schools. He studied Physical Organic Chemistry at the University of Pennsylvania (BA,1963) and Medicine at Johns Hopkins (M.D.,1967). He further trained in Medicine and Microbiology at the University of Chicago. His Ph.D. research with Roizman described the bio-physical properties of the first intact Herpes Virus genomes and the relatedness between the Herpes Simplex 1 and 2 genomes. In 1971, he was appointed Assistant Professor and Director of Infectious Disease at the University of Chicago. He assembled an outstanding Infectious Disease teaching and research Program. His research focused on the Herpes Virus, which Epstein had discovered in African Burkitt Lymphomas and the Henle and Pope labs had discovered could convert human B lymphocytes to perpetually proliferating lymphoblasts (1971).

Dr. Kieff is internationally recognized for his landmark discoveries in elucidating the molecular pathogenesis of EBV infection and lympho-proliferative diseases. His trainees purified EBV, extracted and characterized the DNA and virion proteins, described the extent of virus genome transcription, mRNAs in latently infected cells and in cells replicating virus, derived the first EBV restriction endonuclease maps and first complete molecular clones of Herpes Virus DNAs (EBV), described the EBV proteins expressed in transformed lymphocytes, and evaluated the activity of these proteins expressed by gene transfer in other cells. His laboratory discovered that the EB nuclear protein-2 (EBNA2) and latent infection membrane protein 1 (LMP1) alter cell transcription, growth, and survival. Using antibodies from Pearson and Thorley-Lawson, his group identified the DNA and RNA encoding the principal EBV outer envelop glycoprotein, expressed the recombinant protein, showed that antibody to the recombinant protein neutralized EBV, and with Ellis and Scolnick, expressed the EBV glycoprotein from a VZV vaccine recombinant. In small scale GSK Phase 2 studies, secreted gp350 appears to protect against mononucleosis. In cryo-immune EM and biochemical studies, his lab showed that EBV initially enveloped at the nuclear membrane is rich in gB, whereas enveloped EBV in the cytoplasm and plasma membrane is deficient in gB and rich in gp350, indicative of a 2 stage envelopment process.

Dr. Kieff was promoted to Professor of Medicine, Microbiology, and Virology at Chicago in 1979. In 1987, his lab moved to Harvard and he became Albee Professor of Medicine, Director of Infectious Disease at the Brigham and Women's Hospital and Professor of Microbiology and Molecular Genetics. He directed the Harvard Virology Program from 1992-2005.

At Harvard, his laboratory und