Selenium Deficiency Causes Flu Virus To Mutate Into More Dangerous Forms

[Guest guest]

(if you are living with a crashed immune system, consider adding selenium to

your diet before flu season starts up again)

Jun 23, 2001 12:39 PDT

Source: University Of North Carolina At Chapel Hill (http://www.unc.edu/)

Selenium Deficiency Causes Flu Virus To Mutate Into More Dangerous Forms

CHAPEL HILL -- Influenza virus that has been passed through mice

deficient in the trace nutrient selenium mutates and emerges from the mice

more virulent than before, a new study shows. While the research was

limited to rodents, it's likely that something similar happens in humans

deficient in selenium and, possibly, in other nutrients, University of North

Carolina at Chapel Hill scientists say. That's because humans and mice

are so similar biologically, and the mice were infected with a human

influenza virus.

A report on the discovery appears in the June 8 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 K. , a doctoral student in

nutrition at UNC. Dr. Orville A. Levander, a research chemist with the

Agricultural Research Service's Beltsville Human Nutrition Research

Center, who specializes in selenium, also contributed to the study.

In April, the scientists reported discovering that inadequate intake of

selenium boosts damage caused by influenza viruses.

" We believe our latest findings are both important and potentially

disturbing

because they suggest nutritional deficiencies can promote epidemics in a

way not appreciated before, " Beck said. " Here we looked at flu virus

because it hospitalizes more than 100,000 people each year in the United

States alone. But what we found conceivably could be true for any RNA

virus -- cold virus, AIDS virus and Ebola virus. "

She and worked with colleagues at the U.S. Department of

Agriculture and the Nestle Research Center in Switzerland. They fed

groups of mice either selenium-deficient or normal diets. Later, they

exposed both groups 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.

The difference between the mice's illnesses was the difference between

mild pneumonia and severe pneumonia, which can be life-threatening, they

said.

Afterward, the researchers analyzed the flu viruses for mutations and

compared those harvested from mice both with normal and with selenium-

deficient diets.

" 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. " What's

rather remarkable to us is that we found most of the mutations in the gene

for the M1 matrix protein, an internal viral protein thought to be

relatively

stable, and we observed 29 nucleotide changes in that gene. All 29 were

identical in three different viral isolates from selenium-deficient mice

studied, and one viral isolate from a selenium deficient mouse showed five

additional mutations. "

In contrast, she said, researchers found only one to three mutations in the

genes for the hemagglutinin or neuraminidase proteins, which are known to

have a high rate of variability. " Once the mutations have occurred, even

mice with normal nutrition are more susceptible to the newly virulent

strain, "

she said. " This work, in conjunction with our earlier work with

coxsackie virus, shows that specific nutritional deficiencies can have a

profound impact on the genome of RNA viruses. Poor nutritional status may

contribute to the emergence of new viral strains and might promote

epidemics. "

Since scientists know that selenium is involved as an anti-oxidant, the UNC

researchers and colleagues believe the changes reflect an oxidative stress

mechanism, 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. 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, she and Levander demonstrated for the first time that a

human virus normally harmless to mice mutates and becomes more

dangerous after infecting selenium-deficient and vitamin E-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 found in China among

children and women of childbearing age living in selenium-poor areas, the

disease has been largely eradicated by dietary supplements of the mineral.

" The fact that we're now seeing 29 mutations in this one segment of the

genome of influenza virus just as a result of nutritional manipulation to me

is

just extraordinary, " Levander said. " This work also suggests that the

virulence of the flu bug is somehow affected by the matrix protein, which

has not been studied extensively in the past. This could be very important. "

Other authors of the paper are Qing Shi, a laboratory technician in

pediatrics at UNC, and Drs. Van Dael, J. Schiffrin,

Blum and Denis Barclay of the Nestle Research Center in

Lausanne, Switzerland. Nestle and the National Institutes of Health, through

a grant to the UNC Clinical Nutrition Research Unit, funded the research.