Nutritionally-induced oxidative stress and viral infection

This study was designed to investigate the effect of selenium (Se) or vitamin C deficiency on the immune response to infection with influenza virus. In the first part of the study, we tested whether Se deficiency would affect the immune response and subsequent lung pathology in mice infected with a virulent, mouse-adapted strain of influenza virus, influenza A/Puerto Rico/8/34. In the second part of the study, we tested whether the deficiency or supplementation of another important nutrient, vitamin C, could affect the immune response to influenza infection. Because mice can synthesize vitamin C, we utilized a gulonolactone knockout mouse (gulo -/-) model for our vitamin C deficiency studies. There were no differences in lung influenza A/PR8/34 viral titers between the Seadequate and the Se-deficient mice, or differences in lung influenza A/Bangkok/1/79 viral titers between the vitamin C-adequate and the vitamin C-deficient mice. However, vitamin C-deficient male mice had a higher lung viral titer when infected with the more virulent influenza A/PR8/34 compared with vitamin C-adequate mice. This difference was not found in the female vitamin C-deficient mice. In addition, the Se- and vitamin C-deficient mice had an altered immune response to influenza virus infection. Although vitamin C deficiency increased lung pathology late post infection in both male and female gulo-/- mice, there was a clear sex difference in the effect of vitamin C deficiency on the immune response, as the difference in the expression of chemokines and cytokines was only observed in male vitamin C-deficient mice. This study demonstrated that a deficiency in either Se or vitamin C can alter the immune response to influenza virus infection, resulting in altered lung pathology. In addition, the sex differences found in the vitamin C-deficient mice suggest a further complexity in the response of the host to antioxidant nutrient deprivation. Clearly, an adequate Se and vitamin C intake is essential for a healthy immune response against infectious disease and other antioxidants cannot fully compensate for their deficiency