Viral evolution as driven by host nutritional selective factors: influence of dietary oxidative stress

The endemic juvenile cardiomyopathy known as Keshan disease occurs in regions of China with poor selenium nutrition, but a role for an infectious agent was suggested by seasonal changes in disease incidence. Mice fed a selenium-deficient diet suffered more heart damage than normal mice when infected with a myocarditic coxsackievirus B3 (CVB3/20). Increased heart damage was also observed when CVB3/20 was inoculated into vitamin E-deficient mice. Feeding diets deficient in either vitamin E or selenium allowed an amyocarditic coxsackievirus (CVB3/0) to become myocarditic. When CVB3/0 was harvested from deficient mice, passed through HeLa cells and inoculated into normal (non-deficient) mice, it retained its increased cardiovirulence. Virus obtained from the selenium-deficient mice contained six nucleotide changes in the genome compared with the input strain. This is the first report of a nutritional deficiency driving changes in a viral genome. Host nutritional status could have important public health implications for the spread of influenza, hepatitis, polio and perhaps even AIDS.