Herpes simplex viruses cause two kinds of infections. On initial infection at the portal of entry into the body, the virus replicates and kills the infected cell (lytic infection). In the course of its replication, the virus infects nerve endings and is transported retrograde to neuronal nuclei of peripheral ganglia where it remains latent (silent) and does not harm the neuron. In some individuals the virus periodically reactivates, and is transported anterograde to a site near the portal of entry where it can cause recurrent lesions.
The focus of the research conducted in this laboratory is on the mechanism by which herpes simplex virus with less than 100 genes takes over a human cell with more than 20,000 genes in both lytic and latent infection.
Current studies on lytic infection indicate that both the virus and the cell have evolved a large number of functions designed to thwart each other’s efforts. The cell attempts to silence viral DNA and preclude the expression of its genes. The virus has evolved a large number of functional domains in its proteins that are designed to silence the cell and prevent it from shutting down the virus. In the course of these studies we have identified both the mechanisms by which the cell attempts to shut down the virus and virus-encoded functions that instead silence the cell and block the activation cellular innate immune responses.
The exciting results of the studies on latent infection are two fold: in peripheral neurons the virus allows itself to be silenced by host repressors. At the same time it has evolved the machinery that enables it to reactivate when the neuron harboring the latent virus is stressed by external stimuli such as fever, UV light or emotional/hormonal stress.
The laboratory has trained approximately 50 graduate students and approximately the same number of post-doctoral fellows. The majority of the trainees are in Universities engaged in research and teaching.
Kalamvoki M, Du T, Roizman B. Cells infected with herpes simplex virus 1 export to uninfected cells exosomes containing STING, viral mRNAs, and microRNAs. Proc Natl Acad Sci U S A. 2014 Nov 18;111(46):E4991-6. (PubMed)
Kalamvoki M, Roizman B. HSV-1 degrades, stabilizes, requires, or is stung by STING depending on ICP0, the US3 protein kinase, and cell derivation. Proc Natl Acad Sci U S A. 2014 Feb 4;111(5):E611-7. (PubMed)
Du T, Zhou G, Roizman B. Modulation of reactivation of latent herpes simplex virus 1 in ganglionic organ cultures by p300/CBP and STAT3. Proc Natl Acad Sci U S A. 2013 Jul 9;110(28):E2621-8. (PubMed)
Zhou G, Du T, Roizman B. The role of the CoREST/REST repressor complex in herpes simplex virus 1 productive infection and in latency. Viruses. 2013 Apr 29;5(5):1208-18. Review. (PubMed)
Du T, Zhou G, Roizman B. HSV-1 gene expression from reactivated ganglia is disordered and concurrent with suppression of latency-associated transcript and miRNAs. Proc Natl Acad Sci U S A. 2011 Nov 15;108(46):18820-4. (PubMed)