Biological Trace Element Research

, Volume 56, Issue 1, pp 5–21 | Cite as

Interacting nutritional and infectious etiologies of Keshan disease

Insights from coxsackie virus B-induced myocarditis in mice deficient in selenium or vitamin E
  • Orville A. Levander
  • Melinda A. Beck


In 1979, Chinese scientists reported that selenium had been linked to Keshan disease, an endemic juvenile cardiomyopathy found in China. However, certain epidemiological features of the disease could not be explained solely on the basis of inadequate selenium nutrition. Fluctuations in the seasonal incidence of the disease suggested involvement of an infectious agent. Indeed, a coxsackievirus B4 isolated from a Keshan disease victim caused more heart muscle damage when inoculated into selenium-deficient mice than when given to selenium-adequate mice. Those results led us to study the relationship of nutritional status to viral virulence. Coxsackievirus B3/0 (CVB3/0), did not cause disease when inoculated into mice fed adequate levels of Se and vitamin E. However, mice fed diets deficient in either Se or vitamin E developed heart lesions when infected with CVB3/0. To determine if the change in viral phenotype was maintained, we passaged virus isolated from Se-deficient hosts, maintained, we passaged virus isolated from Se-deficient hosts, designated as CVB3/0 Se-, back into Se-adequate hosts. The CVB3/0 Se- virus caused disease in Se-adequate mice. To determine if the phenotype change was due to changes in the viral genome, we sequenced viruses isolated from Se-deficient mice and compared them with the input CVB3/0 virus. Six point mutations differed between the parent strain and the recovered CVB3/0 Se- isolates. When the experiment was repeated using vitamin E-deficient mice, the same 6 point mutations were found. This is the first report of a specific host nutritional deficiency altering viral genotype. Keshan disease may be the result of several interacting causes including a dominant nutritional deficiency (selenium), other nutritional factors (vitamin E, polyunsaturated fatty acids), and an infectious agent (virus).

Index Entries

Selenium vitamin E cardiomyopathy myocarditis Keshan disease coxsackie virus viral evolution quasispecies oxidative stress infection 


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Copyright information

© Humana Press Inc. 1997

Authors and Affiliations

  • Orville A. Levander
    • 1
  • Melinda A. Beck
    • 2
  1. 1.Nutrient Requirements and Functions Laboratory, Beltsville Human Nutrition Research Center, U.S. Department of AgricultureARSBellsville
  2. 2.Frank Porter Graham Child Development CenterUniversity of North Carolina at Chapel Hill

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