A multi-institutional study reports an effective treatment approach to inhibit and keep latent viruses like herpes simplex from reactivating and causing disease. The work, whose lead author is the late James Hill, PhD, LSU Health New Orleans professor and director of pharmacology and infectious disease at the LSU Eye Center, is published in the Dec. 3, 2014, issue of Science Translational Medicine.
The research team, led by Thomas M. Kristie, PhD, Chief of the Molecular Genetics Section in the National Institute of Allergy and Infectious Diseases' Laboratory of Viral Diseases, and also included Timothy Foster, PhD, LSU Health New Orleans Associate Professor of Microbiology, Immunology & Parasitology, studied herpes simplex virus (HSV) infection in several animal models. They found that an existing drug, tranylcypromine (TCP), blocked a protein called LSD1, which plays a major role in the initiation of herpes simplex virus infection.
Current treatments require active viral replication and target late stages of infection, which has led to the development of drug resistance. This study took a different approach -- targeting a drug to a protein that controls how genes are turned on and off, early in the viral replication process. This "epigenetic" approach not only reduced symptoms, but unlike existing treatments, also reduced shedding (the release of virus particles which can transmit the virus even in the absence of symptoms) and forced the virus to remain in a latent stage, preventing its reactivation. Results indicate that even when a virus is not active, drugs modulating epigenetic changes can still treat the infection. Researchers have been pursuing epigenetic-based therapies for cancer, and this study demonstrates its potential as effective antiviral therapy, too.
A high percentage of the human population is infected with the herpes simplex virus and carries the virus in a latent state. After the initial infection, HSV typically goes dormant in cells where it remains. It can then reactivate with a recurrence of symptoms. Even when latent, asymptomatic shedding of the virus continues its transmission. Neonatal HSV infections can result in death or developmental-neurological issues. HSV eye infections and recurrences are the leading viral cause of infectious blindness or the need for corneal transplants. In addition, along with other herpesviruses, HSV is a complicating factor in immunosuppressed individuals and is a cofactor in HIV transmission.
Although he died before the study was published, LSU Health New Orleans professor Dr. James M. Hill participated in the research. "Dr. Hill was a distinguished and respected herpesvirologist/animal model scientist who passed away approximately a year ago," notes Foster. "He is lead author on this manuscript due to both his contributions to the work and out of honor and respect for his contributions to the field and all of us involved."
In addition to researchers from the National Institutes of Health and LSU Health New Orleans, scientists from the Food and Drug Administration, Harvard Medical School, Cincinnati Children's Hospital Medical Center and the University of Alabama Birmingham also participated. The research was supported by grants from the National Institute of Allergy and Infectious Diseases, National Eye Institute, Research to Prevent Blindness Senior Investigator Award, LSU Health Sciences Center New Orleans, the Louisiana Lions Eye Foundation and U.S. Food and Drug Administration Intramural Funding.
Source: LSU Health Sciences Center New Orleans