Grant: Operating Grant

Vitamins are among the most common health products used, often in mega-doses. However, relatively little is known about the mechanisms of vitamin action in either health or disease. Vitamin A has powerful effects on the eyes, on tissue repair and in maintaining immunity. Large doses of vitamin A are routinely used in developing world infants to prevent blindness and to improve resistance to childhood infections, particularly viral diseases like measles. Measles is a member of a group of viruses that cause serious disease in humans throughout the world including mumps, respiratory syncytial virus (RSV) and the paramyxoviruses. The last agents are responsible for a large proportion of the childhood hospitalizations in Canada and may be involved in the development of asthma. Despite these benefits, recent work has demonstrated that vitamin A and other retinoids do not always have positive effects. Several studies have shown that vitamin A supplements can actually make some virus infections worse. We have shown that retinoids can inhibit the growth of several members of this virus family in the laboratory and we have developed animal models for studying vitamin A-virus interactions. Most recently, we have shown that vitamin A supplements can relieve ferrets of many of the symptoms of severe canine distemper virus infection (CDV or 'dog measles'). We have identified key pathways that retinoids use to protect individual cells (and possibly animals) from these infections. We propose to expand these studies to better understand which of the childhood viruses are susceptible to inhibition by retinoids and which might be made worse by exposure to retinoids. We will study this interaction at multiple levels; from the genes activated by viruses and retinoids all the way to animal models of disease. This knowledge will be critical to pursue improved treatments for these infections and may also give insight into the targeted use of vitamin A supplements.