Respiratory Syncytial Virus Inhibits a Critical Lung Anti-Inflammatory Protein

They reported in the March 4, 2011, online edition of the American Journal of Respiratory and Critical Care Medicine that Nrf2 (nuclear factor (erythroid-derived 2)-like 2) expression was significantly reduced in the children's lung tissue and in the lungs of viral infected mice. Reduction in Nrf2 activity induced a significant decrease in the expression and/or activity of SOD (superoxide dismutase), catalase, GST (glutathione S-transferase), and GPx (glutathione peroxidase). Furthermore, markers of oxidative damage correlated with severity of clinical illness in RSV-infected infants.

Nrf2 is a transcription factor, which in humans is encoded by the NFE2L2 gene. Nrf2 is a master regulator of the antioxidant response, which is important for the amelioration of oxidative stress. Oxidative stress can result in cancer, cardiovascular diseases, inflammation, neurological diseases, and renal disease. Because Nrf2 is able to induce genes important in combating oxidative stress, thereby activating the body's own protective response, it is able to protect from a variety of oxidative stress-related complications, even in situations where the administration of exogenous antioxidants (such as Vitamin C and Vitamin E) have failed.

"What was really striking is that Nrf2 is a kind of master switch controlling the machinery of these antioxidant enzymes, and it appears the virus blocks its activity,” said senior author Dr. Roberto Garofalo, professor of pediatrics, microbiology, and immunology at the University of Texas Medical Branch. "This is interesting because genetic factors have been shown to be associated with other airway diseases, and the obvious question now is do the children who develop the most severe disease in response to RSV also have an Nrf2 gene that favors a low level of expression of these antioxidant enzymes? Are we seeing a combination of two hits, one from the virus, and one from genetics?”

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University of Texas Medical Branch