Emory Report

May 8, 2000

 Volume 52, No. 32

Jones discovers new weapon against flu

by Holly Korschun

At the recent Experimental Biology 2000 meeting in San Diego, Emory scientists reported that glutathione, a naturally occurring antioxidant compound, could help prevent infection by the influenza virus if administered directly (via a lozenge or spray, for example) to the tissues lining the mouth and upper airway.

Glutathione occurs naturally in a variety of foods and has been shown in research studies to reduce cellular damage from a variety of cancer-causing agents, including ionizing radiation and environmental carcinogens.

But in studies on the potential role of dietary glutathione, Dean Jones, professor of biochemistry in the School of Medicine, and his colleagues found that the body does not appear to use the compound on a systemic basis to ward off diseases.

While studying the role of glutathione as an anti-cancer agent, the scientists discovered that one of the enzymes that uses glutathione to detoxify cancer-causing chemicals and oxidants is deposited in the mucous layer lining the mouth and nose, thus providing an extracellular barrier to toxic chemicals. This led them to consider a possible role for glutathione as an anti-flu protectant.

The flu virus is normally released from infected cells as an inactive particle. To infect another cell, it must be activated by having one of its proteins cleaved (split into two pieces) by a protease enzyme. Proteases, along with proteins that normally inhibit their activation, are present in the fluid that lines the epithelial cells in the mouth, upper airways and intestine. Scientists have found through studies in mice that viral infections result in oxidative responses that inactivate natural protease inhibitors, thus enhancing viral activation. They also have found that activation of the virus particles could be controlled by oxidation-reduction reactions.

Knowing that glutathione is an antioxidant and that it is present in the mouth and nose linings, Jones exposed normal human airway epithelial cells in culture to flu virus, both with and without glutathione, in order to test its protective ability against the flu. With high concentrations of flu virus, the glutathione showed no protective effect, but with lower concentrations similar to the amount present during a normal human flu infection, the cells were completely protected against infection.

Jones then infected two groups of mice with a mouse-adapted strain of a human influenza virus. The mice that had been given drinking water containing glutathione had a significant decrease in viral production.

"It appears that by going directly to the site of infection, we can block the influenza infection in the upper airway," Jones said. "We believe that if we put the glutathione in a lozenge, we could directly expose the virus-susceptible tissues to glutathione over a relatively long period of time. This could be very helpful, for example, if you were sitting next to someone with the flu on an airplane. You could effectively block the infection for a period of several hours."

Although the data suggest that a glutathione lozenge would probably work, the concept should be tested in humans, Jones said. And a glutathione lozenge should not be considered an alternative to taking the flu vaccine.

"There is a natural variation among people in resistance to viruses and in our natural antioxidant system," he explained. "If we are smokers, if we are deficient in antioxidant vitamins, if we are under stress, or as we become older, we become more oxidized, which makes us more vulnerable to viral infection. This direct exposure to glutathione could be part of an overall strategy to enhance our antioxidant defenses."

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