Bernard Roizman, ScD Bernard Roizman
Molecular Biology of Herpes simplex Viruses

Professor Emeritus, Molecular Genetics and Cell Biology, Biochemistry and Molecular Biology, Committee on Genetics, Joseph Regenstein Chairman, Committee on Microbiology, Distinguished Srvc. Professor
Sc.D., Johns Hopkins, 1956


Research Summary

My laboratory works on 3 projects involving the biology of herpes simplex viruses (HSV). Project 1 concerns the basic life-style of the virus. In brief, the virus replicates at the portal of entry into the body and concurrently is transported retrograde to peripheral sensory ganglia innervating the site of infection and where it remains silent (latent). The fundamental question we posed is how a virus primed to replicate in virtually any cell is totally silenced in peripheral neurons. The fundamental discovery underlying our studies is that viral DNA is coated by repressive histones and modified by specific repressors immediately upon entry into a susceptible cell. HSV imports along with viral DNA a key viral protein that initiates sequential gene derepression at the portal of entry but this protein is not transported to the neuronal nucleus. The specific repressor complex resident in ganglia initiates the process of sequestering viral DNA into a facultative chromatin-like structure. Recently we reported that a totally novel mechanism reactivates the virus from latent state to cause recurrent herpetic lesions. While we have identified the process of reactivation, the underlying mechanism is under study. Project 2 centers on the finding that HSV encodes a large number of functions designed to block host response to infection. One of these functions is an RNAse that targets mRNAs. Contrary to a lot of publications, the RNase activity was thought to be nonspecific. We have shown that in fact the RNase differentiates between different classes of host mRNAs. It differentiates and degrades by different mechanisms stable host mRNAs GAPDH, actin, etc) and the host stress response, A-U rich mRNAs. Current studies show that the RNase largely spares viral mRNAs. Project 3 involves design and construction of viruses that target cancer cells. We have pioneered the design and construction of these viruses.

Selected Publications

Du, T., Zhou, G., and Roizman, B. Induction of apoptosis accelerates reactivation of latent herpes simplex virus in ganglionic organ cultures and viral replication in cell cultures. Proc. Nat Acad. Sci. (USA) 109: 14616-14621, 2012. (PubMed)

Du, T., Zhou, G., and Roizman, B. HSV-1 gene expression from reactivated ganglia is disordered and concurrent with suppression of latency associated transcript and miRNAs. Proc. Nat. Acad. Sci. (USA) 108: 18820-18824, 2011. (PubMed)

Roizman, B. The checkpoints of viral gene expression in productive and latent infection: The role of the HDAC/CoREST/LSD1/REST repressor complex. J. Virol. 85: 7474-7482, 2011. (PubMed)

Kalamvoki, M., and Roizman, B. The histone acetyl transferase CLOCK is an essential component of the herpes simplex virus 1 transcriptome that includes TFIID, ICP4, ICP27 and ICP22. J. Virol. 85:9472-9477, 2011. (PubMed)

Du, T., Zhou, G., Khan, S., Gu, H., and Roizman B. Disruption of HDAC/CoREST/REST repressor by dnREST reduces genome silencing and increases virulence of herpes simplex virus. Proc. Nat. Acad. Sci (USA) 107:15904-15909, 2010. (PubMed)

Gu, H., and Roizman, B. Herpes simplex virus ICP0 blocks the silencing of viral DNA by dissociating HDACs from the CoREST/REST complex. Proc. Nat. Acad. Sci. (USA) 104: 17174-17139, 2007. (PubMed)

Sciortino, M-T., Taddeo, B., Giuffrè-Cuculletto, M., Medici, M-A, Mastino, A., and Roizman, B. Replication competent herpes simplex virus 1 isolates selected from cells transfected with a BAC-DNA lacking solely the UL49 gene vary with respect to the defect in the UL41 gene encoding host shutoff RNase. J.Virol. 81:10924-10932, 2007. (PubMed)

Zhou, G., Ye, G-J., Debinski, W., and Roizman, B. Engineered herpes simplex virus 1 is dependent on the IL13Rα2 receptor for entry into cells and independent of glycoprotein D receptor interaction. Proc. Nat. Acad. Sci. (USA) 99:15124-15129, 2002. (PubMed)


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