Rodeheffer Carey, von Messling Veronika, Milot Sylvain, Lepine François, Manges Amee R, Ward Brian J
McGill University Health Centre Research Institute, Faculty of Medicine, Division of Infectious Diseases, Montreal General Hospital, Montreal, QC, Canada.
J Nutr. 2007 Aug;137(8):1916-22. doi: 10.1093/jn/137.8.1916.
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.
麻疹病毒（MV）每年导致五十万儿童死亡。维生素A补充剂可显著降低与麻疹相关的死亡率和发病率。维生素A对抗MV的作用机制尚不清楚，目前也没有令人满意的MV感染小动物模型。我们报告了一种雪貂模型的开发，用于研究维生素A对犬瘟热病毒（CDV）的抗病毒活性。CDV在分子水平上与MV密切相关，雪貂的犬瘟热类似于人类的麻疹。我们用CDV感染了维生素A充足（对照）和维生素A缺乏的雪貂，并评估了高剂量维生素A补充剂对CDV疾病的影响能力。在对照雪貂中，CDV感染引起发热、皮疹、结膜炎、咳嗽、鼻炎和腹泻。相比之下，给予30毫克维生素A的对照雪貂在感染后未出现典型的犬瘟热，仅表现出轻微皮疹。该补充剂对雪貂健康没有负面影响，血清和肝脏维生素A浓度增加了100%。我们还发现，雪貂可诱导出严重的维生素A缺乏，高剂量补充维生素A后可迅速逆转。无论是否感染CDV，维生素A缺乏都会导致厌食、腹泻、白内障、行为异常，最终导致死亡。然而，所有接受维生素A补充剂的雪貂都从CDV感染中顺利康复。这些结果重现了人类麻疹维生素A治疗观察的许多方面，并表明雪貂的CDV感染是研究维生素A抗病毒机制的合适模型。
