title: Decreased selenoprotein expression alters the immune response during influenza virus infection in mice.
abstract: Previous work from our laboratory 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 carrying a mutant selenocysteine (Sec) tRNA ([Ser]Sec) transgene (t-trspi(6)A(-)). The levels of selenoproteins are decreased in these mice in a protein- and tissue-specific manner. Male t-trspi(6)A(-) and wild-type (WT) mice were infected with influenza and killed at various time points postinfection (p.i.). Lung mRNA levels for innate and pro-inflammatory cytokines increased with infection but did not differ between groups. However, at d 2 p.i., chemokine levels were greater in the t-trspi(6)A(-) mice compared with WT mice. Additionally, IFN-gamma was higher at d 7 p.i. in the t-trspi(6)A(-) mice and viral clearance slower. Despite these immune system changes, lung pathology was similar in t-trspi(6)A(-) and WT mice. (75)Se labeling experiments demonstrated that glutathione peroxidase (GPX)-1 and thioredoxin reductase, although greatly diminished in the lungs of t-trspi(6)A(-) mice, were not altered as a result of infection. GPX-1 activity in the lungs of the t-trspi(6)A(-) mice was approximately 82% of the WT mice. In addition, the GPX-1 activity in the lungs of Se-deficient mice was 125% less than in the t-trspi(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 during influenza infection.
authors.affiliation: Department of Nutrition, University of North Carolina, Chapel Hill, NC 27599, USA.
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Sheridan
authors.forename: Nianxin
authors.initials: N
authors.lastname: Zhong
authors.forename: Bradley A
authors.initials: BA
authors.lastname: Carlson
authors.forename: Christine M
authors.initials: CM
authors.lastname: Perella
authors.forename: Dolph L
authors.initials: DL
authors.lastname: Hatfield
authors.forename: Melinda A
authors.initials: MA
authors.lastname: Beck
mesh_terms: D000818:Animals; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology* / Q000302:isolation & purification; D008168:Lung / Q000473:pathology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009975:Orthomyxoviridae / Q000276:immunology*; D009976:Orthomyxoviridae Infections / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D012345:RNA, Transfer, Amino Acid-Specific / Q000235:genetics* / Q000276:immunology; D051140:Selenoproteins / Q000096:biosynthesis* / Q000378:metabolism / Q000502:physiology; D014018:Tissue Distribution
chemical_list: D016207:Cytokines; D012345:RNA, Transfer, Amino Acid-Specific; D051140:Selenoproteins; C036928:tRNA, selenocysteine-