Keshan disease

Keshan disease is a cardiomyopathy that manifests in Chinese populations having low selenium intake. After the late 1970s, when the relationship between Keshan disease and selenium was established, selenium supplementation of susceptible individuals substantially reduced the incidence of Keshan disease. However, selenium deficiency did not fully explain the occurrence of the disease, and it was later found that a viral co-factor, coxsackievirus, was necessary for development of the disease.28 Beck and co-workers demonstrated that selenium-deficient mice infected with a harmless strain of coxsackievirus developed inflammation of the heart muscle, whereas selenium-replete mice did not. This was suspected to result from decreased GPx activity, as selenium-deficient mice had a fivefold reduction in GPx activity.34 Confirmation of the role of GPx came through the use of GPx-1 knockout mice, displaying optimal activity of all other selenoenzymes. Infection of the knockout mice with the same strain of coxsack-ievirus also induced myocarditis, as was found in selenium-deficient mice.35 Interestingly, when selenium-replete mice were infected with the virus isolated from selenium-deficient mice, they too developed myocarditis. The virus was shown to mutate to a more virulent strain in selenium-deficient mice. In contrast, no nucleotide changes were found in virus isolated from selenium-replete mice.28

The possibility that oxidative stress may induce changes in viral RNA has implications for many other diseases. Beck and colleagues also examined the effect of selenium on influenza virulence, and found that genes associated with viral replication had at least 29 nucleotide changes in selenium-deficient mice, compared with no changes in selenium-replete mice.36

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