We recently established that fasted young, male ferrets, fed small amounts of arginine deficient (AD) diet develop hyperammonemia and encephalopathy within 2-3 hours. When infected intranasally with influenza B virus before fasting, such ferrets exhibited an extended and more severe encephalopathy with higher mortality rates. Aspirin treatment of infected ferrets, followed by AD diet caused rapidly developing encephalopathy progressing to coma and usually death. Many of the clinical, metabolic and histopathological disorders, commonly observed in Reye's Syndrome (RS) were noted in these ferrets. Using the conditions described, we have produced an animal model for RS. We plan to (1) further characterize the model, (2) identify and study the mechanism of action of host and environmental factors that can influence the duration, severity and outcome of the induced animal disorders, (3) determine the sequence of biochemical and histopathological changes associated with the development of animal disorders, (4) test various RS-related viruses and viral strains to determine whether severity of their effect on the model are related to other viral characteristics and to quantitative aspects of infection, including tropism, and (5) use the animal work to guide patient studies designed to improve diagnosis and management and to test treatment protocols.
