UC scientists discover protein that reactivates herpes simplex virus, solve medical mystery

Researchers at the University of Cincinnati and Cincinnati Children's Hospital Medical Center have helped to solve an old medical mystery.Their findings, done in collaboration with the Medical Research Council Virology Unit of Glasgow, Scotland, were published in the Public Library of Science (PLoS) Pathogens.  The team of researchers has identified PV16, a viral protein that triggers the herpes simplex virus (HSV) out of latency and into recurrent outbreaks."Our current findings show that, in elegant simplicity, the herpes simplex virus regulates this complex lifecycle through the expression of VP16," says Nancy Sawtell, PhD, author and researcher in the division of infectious diseases at Cincinnati Children’s Hospital Medical Center and associate professor in UC's pediatrics department. The idea that HSV manifested as either latent or active was proposed 80 years ago.  On the body's surface, the virus replicates itself into thousands of copies that can be passed to other people via contact.  However, on the level of neurons, HSV's genetic code goes into hiding for the lifetime of the carrier.There are no ways to prevent, cure or stop this highly contagious virus from exiting latency at present.  But with these new findings, researchers are hopeful this could improve with further study.The researchers made their discovery by conducting a high fever simulation on a mouse model with HSV.  With the high fever, the latent virus became active.  Fevers have long been associated with triggering the reactivation of HSV in the form of cold sores.The high fever correlated with a random de-repression of VP16, causing the reactivation of the virus."This completely changes our thinking about how this virus reactivates from latency," said Richard Thompson, PhD, co-author and researcher in the department of molecular genetics, biochemistry and microbiology at UC.  "Instead of a simple positive switch that turns the virus on following stress, it appears instead to be a random de-repression of the VP16 gene that results in reactivation." This promising research could lead to improved molecular treatments for HSV as well as refined engineering of strands of HSV used in cancer therapy.Funding for this study came from the National Institutes of Health. Writer:  Jonathan DeHartSource:  Wendy Beckman, University of Cincinnati