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Nutrition and Disease

Disease Manifestations of Canine Distemper Virus Infection in Ferrets Are Modulated by Vitamin A Status^1,2

³ McGill University Health Centre Research Institute, Faculty of Medicine, Division of Infectious Diseases, Montreal General Hospital, Montreal, QC, Canada; ⁴ Institut National de la Recherche Scientifique-Institut Armand Frappier, Université du Québec, Laval, QC, Canada; ⁵ Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, QC, Canada

^* To whom correspondence should be addressed. E-mail: brian.ward{at}mcgill.ca.

The measles virus (MV) causes half a million childhood deaths annually. Vitamin A supplements significantly reduce measles-associated mortality and morbidity. The mechanisms whereby vitamin A acts against MV are not understood and currently there is no satisfactory small animal model for MV infection. We report on the development of a ferret model to study antiviral activity of vitamin A against canine distemper virus (CDV). CDV is closely related to MV at the molecular level and distemper in ferrets mimics measles in humans. We infected vitamin A-replete (control) and vitamin A-depleted ferrets with CDV and assessed the ability of high-dose vitamin A supplements to influence CDV disease. In control ferrets, CDV infection caused fever, rash, conjunctivitis, cough, coryza, and diarrhea. In contrast, control ferrets that were given 30 mg of vitamin A did not develop typical distemper after infection and exhibited only a mild rash. The supplement did not negatively affect ferret health and resulted in a 100% increase in serum and liver vitamin A concentrations. We also found that profound vitamin A deficiency is inducible in ferrets and can be rapidly reversed upon high-dose vitamin A supplementation. Vitamin A deficiency caused anorexia, diarrhea, cataracts, behavioral abnormalities, and ultimately death, with or without CDV infection. All ferrets that received vitamin A supplements, however, recovered uneventfully from CDV infection. These results replicate many aspects of the observations of vitamin A therapy in humans with measles and suggest that CDV infection in ferrets is an appropriate model for the study of the antiviral mechanism of vitamin A.

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