Research Summary

Herpes simplex viruses are large DNA pathogens encoding at least 84 proteins. Our research focuses on the molecular biology of these viruses and in particular on two areas: The first concerns the mechanisms by which the virus subjugates the infected cell, evades host responses, and makes the cell produce many thousands of virus particles. Current studies center on the functions of several proteins. One, a multifunctional protein designated ICP0 acts as very unusual ubiquitin ligase that targets cellular proteins potentially inimical to the virus. Most E2 enzymes have a single ubiquitin ligase site whereas ICP0 has two sites interacting with different ubiquitin conjugating enzymes. Another viral protein, ICP22, scavenges the cell for a cellular protein that it uses to regulate viral gene expression. In addition, three other viral proteins that include two glycoproteins and a protein kinase block the cell from attempting to commit suicide (apoptosis) possibly in a vain attempt to sacrifice itself to preclude viral multiplication. One component of these studies consists of analyses of the mechanisms by which the virus blocks host responses consisting of mRNA induced after infection from being expressed in the infected cell. The second area of research is based on the accumulated knowledge regarding viral gene functions and the ability to genetically engineer novel viruses. Our objective is to make novel viruses that specifically target cancer cells and selectively destroy them without affecting normal cells. These studies have generated highly promising results and may lead to the transformation of a human pathogen into a therapeutic agent.

Selected Publications

Hagglund, R., Van Sant, C., Lopez, P., and Roizman B. Herpes simplex virus 1 infected cell protein 0 contains two E3 ubiquitin ligase sites specific for different E2 ubiquitin conjugating enzymes. Proc. Nat. Acad. Sci. (USA) 99:631-666, 2002. (PubMed)

Sciortino, M.T, Taddeo, B., Mastino, A., and Roizman, B. Of the three tegument proteins that package mRNA in herpes simplex virions, one (VP22), transports the mRNA to uninfected cells for expression prior to viral infection. Proc. Nat Acad. Sci. (USA) 99:8318-8323, 2002. (PubMed)

Zhou, G , Guo-Jie Ye, G-J., Debinski, W. and Roizman, B. Genetic engineering of a herpes simplex virus 1 vector dependent on the IL13R 2 receptor for entry into cells: interaction of glycoprotein D with its receptors is independent of the fusion of the envelope and the plasma membrane. Proc. Nat. Acad. Sci. (USA) 99:15124-15129, 2002. (PubMed)

Zhou, G., and Roizman, B. The truncated forms of glycoprotein D of herpes simplex virus 1 capable of blocking apoptosis and of low efficiency entry into cells form a heterodimer dependent on the presence of a cysteine located in the shared transmembrane domains. J. Virol. 76:11469-11475, 2002. (PubMed)