INTERACTING NUTRITIONAL AND INFECTIOUS ETIOLOGIES OF KESHAN-DISEASE -INSIGHTS FROM COXSACKIE-VIRUS-B-INDUCED MYOCARDITIS IN MICE DEFICIENTIN SELENIUM OR VITAMIN-E

In 1979, Chinese scientists reported that selenium had been linked to Keshan disease, an endemic juvenile cardiomyopathy found in China. How ever, certain epidemiological features of the disease could not be exp lained solely on the basis of inadequate selenium nutrition. Fluctuati ons in the seasonal incidence of the disease suggested involvement of an infectious agent. Indeed, a coxsackievirus B4 isolated from a Kesha n disease victim caused more heart muscle damage when inoculated into selenium-deficient mice than when given to selenium-adequate mice. Tho se results led us to study the relationship of nutritional status to v iral virulence. Coxsackievirus B3/0 (CVB3/0), did not cause disease wh en inoculated into mice fed adequate levels of Se and vitamin E. Howev er, mice fed diets deficient in either Se or vitamin E developed heart lesions when infected with CVB3/0. To determine if the change in vira l phenotype was maintained, we passaged virus isolated from Se-deficie nt hosts, designated as CVB3/0 Se-, back into Se-adequate hosts. The C VB3/0 Se- virus caused disease in Se-adequate mice. To determine if th e phenotype change was due to changes in the viral genome, we sequence d viruses isolated from Se-deficient mice and compared them with the i nput CVB3/0 virus. Six point mutations differed between the parent str ain and the recovered CVB3/0 Se- isolates. When the experiment was rep eated using vitamin E-deficient mice, the same 6 point mutations were found. This is the first report of a specific host nutritional deficie ncy altering viral genotype. Keshan disease may be the result of sever al interacting causes including a dominant nutritional deficiency (sel enium), other nutritional factors (vitamin E, polyunsaturated fatty ac ids), and an infectious agent (virus).