Jeffrey Cohen joined the Medical Virology Section of the Laboratory of Clinical Investigation, NIAID, in 1991 and is now a Senior Investigator there. He re-ceived his M.D. from Johns Hopkins in 1981.

My laboratory focuses on the molecular pathogenesis of human herpes viruses. The major approach has been to probe viral-gene functions by deleting or mutating target sequences within the genomes. I developed a system to produce mutations in the Epstein-Barr virus (EBV) genome by transfecting cells with cosmid DNAs to obtain recombinant viruses. Using this system, I showed that the EBV nuclear antigen-2 (EBNA-2) protein is required for B-cell transformation by the virus. Further experiments identified the specific domain of the EBNA-2 protein that is responsible for activating transcription. By deleting this domain or replacing the domain with a transactivating region from herpes simplex virus VP16 protein, we demonstrated that this domain is required for transformation of B cells by EBV. In more recent experiments, we inoculated mice with severe combined immunodeficiency with a panel of EBV mutants that differ in their EBNA-2 sequences. The pattern of EBV-induced tumor formation in the mice paralleled the ability of the mutants to transform cells in vitro. Currently, my research focuses on EBV genes that help the virus to evade host immune responses.

Last year we reported on an in vitro system for producing a recombinant form of the varicella-zoster virus (VZV), which causes chicken pox. We constructed a set of four cosmids that encompass the 125-kb VZV genome. Transfection of cells in culture with these four cosmids results in recombination and production of infectious VZV. Using this system, we introduced mutations into the viruses, which are being tested in a guinea pig model of VZV infection. In addition, a herpes simplex virus glycoprotein gene was inserted into the VZV genome, and the recombinant VZV functioned as a vaccine to protect guinea pigs from challenge with herpes simplex. The VZV strain under study is the live, attenuated vaccine virus that may be approved for universal immunization of children in the United States. This vaccine strain becomes latent in the body and, unfortunately, can reactivate to produce herpes zoster (shingles). We are trying to define which viral gene(s) may be responsible for development of latency or reactivation. By inducing mutations in these latency-associated genes, we may be able to produce a safer vaccine that cannot reactivate and cause shingles.


David Bodine, NCHGR
John Cidlowski, NIEHS
Seong-Jin Kim, NCI
Stephen Wank, NIDDK
Lois Travis, NCI

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