Scientists: nutritional deficiency can boost influenza virus damage

April 26, 2001

CHAPEL HILL -- University of North Carolina at Chapel Hill researchers have found strong new evidence to support what concerned mothers have preached for generations: Eating a balanced diet can be critical to good health. The scientists have discovered that inadequate intake of selenium, a trace mineral, boosts damage caused by influenza viruses.

Working with others at the USDA's Agricultural Research Service in Beltsville, Md., and the Nestle Research Center in Switzerland, the UNC virologists fed groups of mice either selenium-deficient or normal diets. They later exposed both groups of mice to a mild strain of human influenza virus known as Influenza A Bangkok.

Rodents consuming too little selenium developed significantly more harmful lung inflammation, which also lasted considerably longer, than animals that developed the flu but whose diets were normal. Since mice and humans are similar in the way they respond to influenza infection, the chance that comparable damage occurs in humans is strong, researchers said. The difference between the mice was the difference between mild pneumonia and severe pneumonia, which can be life threatening, they said.

A report on the discovery appears in the April 27 issue of the FASEB Journal, a scientific journal published by the Federation of American Societies for Experimental Biology. Authors include Dr. Melinda A. Beck, associate professor of pediatrics and nutrition at the UNC schools of medicine and public health, and Heather K. Nelson, a doctoral student in nutrition at UNC. Dr. Orville A. Levander, a nutritionist with the Agricultural Research Service's Beltsville Human Nutrition Research Center, who specializes in selenium, also contributed to the study.

"It's been known for a long time that if you're malnourished, you're more susceptible to infectious diseases, and so it's not really remarkable that the mice would be sicker when they have a deficiency," Beck said.

"We looked at specific elements of the mice's immune systems that were associated with the increase in pathology and found certain changes," she said. "What that suggests is that the deficiency in selenium altered their immune response, and so they got sicker than they would normally. This shows you need to have a balance in all the essential nutrients, and that a deficiency in one can have a profound effect."

The new work lays the groundwork for demonstrating that a specific deficiency in a specific nutritional requirement can affect the immune system and then affect viral infections, Beck said. It helps pinpoint how the deficiency matters.

"Since we know that selenium is involved as an anti-oxidant, we think we're looking at an oxidative stress mechanism here," she said. "It might be that any kind of oxidative stress to the host produces a similar effect, but we won't know that for sure until we look at other anti-oxidants."

Selenium is a component of glutathione perioxidase (GPX), an anti-oxidant enzyme the body uses to combat oxidative stress, she said. Without selenium, GPX activity, which she and her colleagues can measure in mice, declines or ceases. One result is a greatly exaggerated, defective immune response. Good sources of selenium include grains such as wheat and rice and meat, and so most people in this country shouldn't worry about supplementing their diets to get it, Beck said.

Five years ago, Beck and Levander demonstrated for the first time that a human virus normally harmless to mice mutates and becomes more dangerous after infecting selenium-deficient mice. Following mutation, the virus can then infect and damage the hearts of mice with no selenium deficiency.

The virus they studied, coxsackie B3, is thought to play a central role in a heart disease known as Keshan disease. Once common in China among children and women of childbearing age living in selenium-poor areas, the disease has been mostly eradicated by dietary supplements of the mineral.
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Other authors of the paper are Qing Shi, a laboratory technician in pediatrics at UNC, and Drs. Peter Van Dael, Eduardo J. Schiffrin, Stephanie Blum and Denis Barclay of the Nestle Research Center in Lausanne, Switzerland. Nestle paid for the research.

Note: Beck and Nelson can be reached at 919-966-6809. Levander's number is 301-504-8504.

University of North Carolina at Chapel Hill

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