Scientists discover influenza’s Achilles heel: Antioxidants

New research in the FASEB Journal opens the door for new drugs that could prevent severe flu-related lung damage

As the nation copes with a shortage of vaccines for H1N1 influenza, a team of Alabama researchers have raised hopes that they have found an Achilles’ heel for all strains of the flu—antioxidants. In an article appearing in the November 2009 print issue of the FASEB Journal (http://www.fasebj.org) they show that antioxidants—the same substances found in plant-based foods—might hold the key in preventing the flu virus from wreaking havoc on our lungs.

“The recent outbreak of H1N1 influenza and the rapid spread of this strain across the world highlights the need to better understand how this virus damages the lungs and to find new treatments,” said Sadis Matalon, co-author of the study. “Additionally, our research shows that antioxidants may prove beneficial in the treatment of flu.”

Matalon and colleagues showed that the flu virus damages our lungs through its “M2 protein,” which attacks the cells that line the inner surfaces of our lungs (epithelial cells). Specifically, the M2 protein disrupts lung epithelial cells’ ability to remove liquid from inside of our lungs, setting the stage for pneumonia and other lung problems. The researchers made this discovery by conducting three sets of experiments using the M2 protein and the lung protein they damage. First, frog eggs were injected with the lung protein alone to measure its function. Second, researchers injected frog eggs with both the M2 protein and the lung protein and found that the function of the lung protein was significantly decreased. Using molecular biology techniques, scientists isolated the segment of the M2 protein responsible for the damage to the lung protein. Then they demonstrated that without this segment, the protein was unable to cause damage. Third, the full M2 protein (with the “offending” segment intact) and the lung protein were then re-injected into the frog eggs along with drugs known to remove oxidants. This too prevented the M2 protein from causing damage to the lung protein. These experiments were repeated using cells from human lungs with exactly the same results.

“Although vaccines will remain the first line of intervention against the flu for a long time to come, this study opens the door for entirely new treatments geared toward stopping the virus after you’re sick,” said Gerald Weissmann, M.D., Editor-in-Chief of the FASEB Journal, “and as Thanksgiving approaches, this discovery is another reason to drink red wine to your health.”

Receive monthly highlights from the FASEB Journal by e-mail. Sign up at http://www.faseb.org/fasebjournalreaders.htm. The FASEB Journal (http://www.fasebj.org) is published by the Federation of the American Societies for Experimental Biology (FASEB). The journal has been recognized by the Special Libraries Association as one of the top 100 most influential biomedical journals of the past century and is the most cited biology journal worldwide according to the Institute for Scientific Information. FASEB comprises 22 nonprofit societies with more than 80,000 members, making it the largest coalition of biomedical research associations in the United States. FASEB advances health and welfare by promoting progress and education in biological and biomedical sciences through service to its member societies and collaborative advocacy.

Details: Ahmed Lazrak, Karen E. Iles, Gang Liu, Diana L. Noah, James W. Noah, and Sadis Matalon. Influenza virus M2 protein inhibits epithelial sodium channels by increasing reactive oxygen species. FASEB J. doi:10.1096/fj.09-135590 ; http://www.fasebj.org/cgi/content/abstract/23/11/3829

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