Virology and Pharmacology Laboratory
One of the strengths of the research division of the LSU Eye Center is our animal models for viral diseases of the eye. Since 1962 when Dr. Herbert Kaufman first proved that idoxuridine could be used to treat patients with herpetic keratitis, the rabbit eye has been an outstanding model for screening antiviral agents. The late Dr. Hill perfected an animal model of HSV reactivation and recurrent disease that can look at the full spectrum of crudescence of herpes simplex virus type 1. Current experiments are focusing on understanding of the molecular basis of HSV reactivation to determine therapeutic strategies that will not only block viral replication, but will prevent the neuronal reactivation, the primary source of the virus. Our studies on the molecular biology of herpes virus include recombinant viruses to study various genome factors within the virus that are responsible for virulence. Our genetic studies using microarrays are analyzing changes in host genome patterns to identify specific proteins involved in neuronal reactivation. Newly developed chromatin immunoprecipitation assays that will allow analysis of the genome virus and protein interactions to test suppression or activation of regions of the genome are ongoing.
In addition, we have constructed recombinant viruses that have different phenotypic reactivations, i.e. very high and very low. We have also constructed recombinant viruses that contain an insert designated the enhanced green fluorescent protein. This allows visualization of the corneal lesions in the eyes of infected animals such as the BALB/c mouse, as well as detecting the virus in neural tissue. Using the molecular tweezers, also known as laser capture microdissection, we can obtain a population of cells that are known to be in a certain metabolic state, that is undergoing reactivation or not undergoing reactivation.
All of these studies have the ultimate goal of preventing recurrent herpetic infection of the eye. The need for this is that only about 40% of patients who are treated with the current antivirals have a blockage of the recurrent disease. That means that over 60% have recurrent diseases that can only be treated by a corneal transplant. Recurrent herpetic keratitis can result in severe stromal disease and, when in the central axis, will reduce visual acuity. All of these studies are designed to develop chemotherapeutic agents that will block the neuronal reactivation. In a broad scheme, if we find that for HSV-1 that we can block neuronal reactivation, we can probably also use the same drugs to block HSV-2 reactivation which is a serious venereal disease problem and also the third virus that makes up the alphaherpesviruses in humans, varicella zoster, not only causes chicken pox mostly in children, but causes shingles in the elderly and it is possible that the agent could work for all three of these clinical conditions that are very serious.