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Decreased selenoprotein expression results in an altered immune response post influenza virus infection
Author(s) -
Sheridan Patricia A,
Carlson Bradley A,
Hatfeild Dolph L,
Beck Melinda A
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a1067-a
Subject(s) - immune system , selenoprotein , biology , genetically modified mouse , influenza a virus , inflammation , chemokine , selenium deficiency , immunology , glutathione peroxidase , virus , glutathione , transgene , enzyme , biochemistry , gene
Previous work in our laboratory has demonstrated that host selenium (Se)‐deficiency results in greater lung pathology and altered immune function in mice infected with influenza virus. Because selenoproteins play a key role in determining the oxidant status of the host, we utilized a transgenic mouse line, Sec tRNA [Ser]Sec (i 6 A), wherein the expressed tRNA product lacks a highly modified nucleoside, isopentenyladenosine (i 6 A), at position 37. The levels of selenoproteins are decreased in these mice in a protein and tissue specific manner. Male i 6 A and wildtype (WT) mice were infected with influenza and sacrificed at 0, 2 and 7 days post infection (p.i.). Lung mRNA levels for innate and pro‐inflammatory cytokines were increased with infection, but did not differ between groups. However, at d3 p.i. chemokine levels were increased in the i 6 A mice compared to WT. Additionally, interferon‐γ was higher at d7 p.i. in the i 6 A mice and viral clearance slower. Despite the immune changes, lung pathology was not different in the i 6 A‐ mice compared with WT mice. 75 Se labeling experiments demonstrated that glutathione peroxidase‐1 (GPx‐1) and thioredoxin reductase (TR), although greatly diminished in the lungs of i 6 A‐ mice, were not altered as a result of infection. GPx‐1 activity in the lungs of the i 6 A mice was approximately 6‐fold less compared with WT mice. In addition, the GPx‐1 activity levels in the lungs of Se‐deficient mice are 10‐fold less than that seen in the i 6 A mice. These results suggest that although selenoproteins are important for immune function, there is a threshold of GPx‐1 activity that can prevent an increase in lung pathology post influenza infection. Supported byNIH grant R01 AI055050 to MAB.