title: Disease manifestations of canine distemper virus infection in ferrets are modulated by vitamin A status.
abstract: 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.
authors.affiliation: McGill University Health Centre Research Institute, Faculty of Medicine, Division of Infectious Diseases, Montreal General Hospital, Montreal, QC, Canada.
authors.forename: Carey
authors.initials: C
authors.lastname: Rodeheffer
authors.forename: Veronika
authors.initials: V
authors.lastname: von Messling
authors.forename: Sylvain
authors.initials: S
authors.lastname: Milot
authors.forename: François
authors.initials: F
authors.lastname: Lepine
authors.forename: Amee R
authors.initials: AR
authors.lastname: Manges
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Ward
mesh_terms: D000818:Animals; D004032:Diet; D019587:Dietary Supplements; D004216:Distemper / Q000503:physiopathology* / Q000821:virology; D004217:Distemper Virus, Canine / Q000187:drug effects / Q000502:physiology*; D005247:Feeding Behavior / Q000187:drug effects; D005260:Female; D005289:Ferrets / Q000821:virology*; D005334:Fever / Q000821:virology; D008297:Male; D023421:Models, Animal; D014801:Vitamin A / Q000378:metabolism* / Q000494:pharmacology*; D014802:Vitamin A Deficiency / Q000139:chemically induced / Q000178:diet therapy
chemical_list: D014801:Vitamin A