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Journal ArticleDOI

Protection from H1N1 influenza virus infections in mice by supplementation with selenium: a comparison with selenium-deficient mice.

Lei Yu1, Lei Sun1, Yi Nan, Li-Ying Zhu1 
01 Jun 2011-Biological Trace Element Research (Humana Press Inc)-Vol. 141, Iss: 1, pp 254-261

TL;DR: The data indicate that selenium supplementation may provide a feasible approach to improving the immune response to viral infections, such as lethal influenza infection.

AbstractThe present paper describes protective effects of supplemental selenium in mice infected with influenza virus. The effects of supplemental selenium on serum selenium levels, mortality, lung virus titers, and cytokine titers were investigated in mice inoculated intranasally with suspensions of influenza virus. Whereas the mortality of the virus-infected Se-deficient mice was 75%, along with a marked reduction in body weight, lower levels of TNF-α and IFN-γ and lower serum selenium concentrations, the mortality of mice maintained on feed containing 0.5 mg Se/kg in the form of sodium selenite was 25%.There were no significantly differences, however, in viral titer between the Se-adequate and the selenium-supplemented groups. The data indicate that selenium supplementation may provide a feasible approach to improving the immune response to viral infections, such as lethal influenza infection.

Topics: Influenza A virus (59%), Selenium deficiency (58%), Selenium (55%), Virus (51%)

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Citations
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Journal ArticleDOI
TL;DR: Particular emphasis is given to how Se and selenoproteins are linked to redox signaling, oxidative burst, calcium flux, and the subsequent effector functions of immune cells, as well as the benefits and potential adverse effects of intervention with Se supplementation for various inflammatory or immune disorders.
Abstract: Dietary selenium (]Se), mainly through its incorporation into selenoproteins, plays an important role in inflammation and immunity. Adequate levels of Se are important for initiating immunity, but they are also involved in regulating excessive immune responses and chronic inflammation. Evidence has emerged regarding roles for individual selenoproteins in regulating inflammation and immunity, and this has provided important insight into mechanisms by which Se influences these processes. Se deficiency has long been recognized to negatively impact immune cells during activation, differentiation, and proliferation. This is related to increased oxidative stress, but additional functions such as protein folding and calcium flux may also be impaired in immune cells under Se deficient conditions. Supplementing diets with above-adequate levels of Se can also impinge on immune cell function, with some types of inflammation and immunity particularly affected and sexually dimorphic effects of Se levels in so...

441 citations


Journal ArticleDOI
TL;DR: The evidence is at present conflicting as to whether Se supplementation is of benefit in patients with HT, though there are indications that it is advantageous in cases of mild/moderate Graves’ Orbitopathy and the role of Se in type 2 diabetes mellitus is ambiguous.
Abstract: This review aims to illustrate the importance of selenium (Se) for maintenance of overall health, especially for the thyroid, immunity, and homeostasis. Furthermore, it outlines the role of Se in reproduction and in virology and discusses the effects of Se supplementation in critical illness. The multifaceted aspects of this essential nutrient have attracted worldwide clinical and research interest in the last few decades. Se exerts its activity in the form of the aminoacid selenocysteine incorporated in selenoproteins. The impact of Se administration should be considered in relation to its apparent U shaped effects, i.e., exhibiting major advantages in Se-deficient individuals but specific health risks in those with Se excess. Addition of selenium to the administration of levothyroxine may be useful in patients with low Se intake and with mild-form or early-stage Hashimoto’s thyroiditis (HT). Serum Se concentration (possibly also at tissue level) decreases in inflammatory conditions and may vary with the severity and duration of the inflammatory process. In such cases, the effect of Se supplementation seems to be useful and rational. Meanwhile, Se’s ability to improve the activity of T cells and the cytotoxicity of natural killer cells could render it effective in viral disease. However, the evidence, and this should be stressed, is at present conflicting as to whether Se supplementation is of benefit in patients with HT, though there are indications that it is advantageous in cases of mild/moderate Graves’ Orbitopathy. The role of Se in type 2 diabetes mellitus (T2DM) is ambiguous, driven by both Se intake and serum levels. The evidence that insulin and glycaemia influence the transport and activity of Se, via regulatory activity on selenoproteins, and that high serum Se may have a diabetogenic effect suggests a ‘Janus-effect’ of Se in T2DM. Though the evidence is not as yet clear-cut, the organic form (selenomethionine), due to its pharmacokinetics, is likely to be more advantageous in long-term prevention, and supplementation efforts, while the inorganic form (sodium selenite) has proven effective in an acute, e.g., sepsis, clinical setting. Recent data indicate that functional selenoprotein single-nucleotide polymorphisms (SNPs) may interfere with Se utilization and effectiveness.

206 citations


Cites background from "Protection from H1N1 influenza viru..."

  • ...Though Se supplementation did not decrease the viral titer, it achieved 50 % reduction of mortality as compared to virus-infected Se-deficient mice, hence providing some evidence that Se supplementation improves the immune response to lethal influenza infection [165]....

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Journal ArticleDOI
TL;DR: This review summarizes the survey of knowledge on selenium nanoparticles, their biological effects in the organism, advantages, absorption mechanisms, and nanotechnological applications for peroral administration and explores the possibilities of a more effective way of administration, especially in seenium-deficient organisms.
Abstract: Traditional supplements of selenium generally have a low degree of absorption and increased toxicity. Therefore, it is imperative to develop innovative systems as transporters of selenium compounds, which would raise the bioavailability of this element and allow its controlled release in the organism. Nanoscale selenium has attracted a great interest as a food additive especially in individuals with selenium deficiency, but also as a therapeutic agent without significant side effects in medicine. This review is focused on the incorporation of nanotechnological applications, in particular exploring the possibilities of a more effective way of administration, especially in selenium-deficient organisms. In addition, this review summarizes the survey of knowledge on selenium nanoparticles, their biological effects in the organism, advantages, absorption mechanisms, and nanotechnological applications for peroral administration.

181 citations


Cites background from "Protection from H1N1 influenza viru..."

  • ...5 mg Se⋅kg−1, and mice with low serum selenium concentrations showed a marked reduction in body weight (BW) and lower levels of TNF-α and IFN-γ.(120) For improving the immune response in the body, the administration of SeNPs can also be an efficient realizable approach....

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  • ...The mortality of the H1N1 influenza virus-infected selenium-deficient mice was 3 times higher compared to those receiving Na 2 SeO 3 at the dose of 0.5 mg Se⋅kg−1, and mice with low serum selenium concentrations showed a marked reduction in body weight (BW) and lower levels of TNF-α and IFN-γ.120 For improving the immune response in the body, the administration of SeNPs can also be an efficient realizable approach....

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Journal ArticleDOI
TL;DR: The results establish Sel K as an endoplasmic reticulum-membrane protein important for promoting effective Ca2+ flux during immune cell activation and provide insight into molecular mechanisms by which dietary selenium enhances immune responses.
Abstract: Selenoprotein K (Sel K) is a selenium-containing protein for which no function has been identified. We found that Sel K is an endoplasmic reticulum transmembrane protein expressed at relatively high levels in immune cells and is regulated by dietary selenium. Sel K−/− mice were generated and found to be similar to wild-type controls regarding growth and fertility. Immune system development was not affected by Sel K deletion, but specific immune cell defects were found in Sel K−/− mice. Receptor-mediated Ca2+ flux was decreased in T cells, neutrophils, and macrophages from Sel K−/− mice compared with controls. Ca2+-dependent functions including T cell proliferation, T cell and neutrophil migration, and Fcγ receptor-mediated oxidative burst in macrophages were decreased in cells from Sel K−/− mice compared with that in cells from controls. West Nile virus infections were performed, and Sel K−/− mice exhibited decreased viral clearance in the periphery and increased viral titers in brain. Furthermore, West Nile virus-infected Sel K−/− mice demonstrated significantly lower survival (2 of 23; 8.7%) compared with that of wild-type controls (10 of 26; 38.5%). These results establish Sel K as an endoplasmic reticulum-membrane protein important for promoting effective Ca2+ flux during immune cell activation and provide insight into molecular mechanisms by which dietary selenium enhances immune responses.

161 citations


Journal ArticleDOI
TL;DR: The formal identification of viral selenoproteins in the genome of molluscum contagiosum and fowlpox viruses demonstrated the importance of selenocsteine in viral cycle.
Abstract: Reactive oxygen species (ROS) are frequently produced during viral infections. Generation of these ROS can be both beneficial and detrimental for many cellular functions. When overwhelming the antioxidant defense system, the excess of ROS induces oxidative stress. Viral infections lead to diseases characterized by a broad spectrum of clinical symptoms, with oxidative stress being one of their hallmarks. In many cases, ROS can, in turn, enhance viral replication leading to an amplification loop. Another important parameter for viral replication and pathogenicity is the nutritional status of the host. Viral infection simultaneously increases the demand for micronutrients and causes their loss, which leads to a deficiency that can be compensated by micronutrient supplementation. Among the nutrients implicated in viral infection, selenium (Se) has an important role in antioxidant defense, redox signaling and redox homeostasis. Most of biological activities of selenium is performed through its incorporation as a rare amino acid selenocysteine in the essential family of selenoproteins. Selenium deficiency, which is the main regulator of selenoprotein expression, has been associated with the pathogenicity of several viruses. In addition, several selenoprotein members, including glutathione peroxidases (GPX), thioredoxin reductases (TXNRD) seemed important in different models of viral replication. Finally, the formal identification of viral selenoproteins in the genome of molluscum contagiosum and fowlpox viruses demonstrated the importance of selenoproteins in viral cycle.

157 citations


Cites background from "Protection from H1N1 influenza viru..."

  • ...↓ GPX activity in infected people [116] AM = KunMing Mice SS = Selenite Reduces mortality, ↑ levels of TNFalpha and IFNgamma No change in viral load [197]...

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References
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18 Aug 2011
Abstract: Lack of adequate macronutrients or selected micronutrients, especially zinc, selenium, iron, and the antioxidant vitamins, can lead to clinically significant immune deficiency and infections in children. Undernutrition in critical periods of gestation and neonatal maturation and during weaning impairs the development and differentiation of a normal immune system. Infections are both more frequent and more often become chronic in the malnourished child. Recent identification of genetic mechanisms is revealing critical pathways in the gastrointestinal immune response. New studies show that the development of tolerance, control of inflammation, and response to normal mucosal flora are interrelated and linked to specific immune mechanisms. Nutrients act as antioxidants and as cofactors at the level of cytokine regulation. Protein calorie malnutrition and zinc deficiency activate the hypothalamic-pituitary-adrenal axis. Increased circulating levels of glucocorticoids cause thymic atrophy and affect hematopoiesis. Chronic undernutrition and micronutrient deficiency compromise cytokine response and affect immune cell trafficking. The combination of chronic undernutrition and infection further weakens the immune response, leading to altered immune cell populations and a generalized increase in inflammatory mediators. Obesity caused by excess nutrition or excess storage of fats relative to energy expenditure is a form of malnutrition that is increasingly seen in children. Leptin is emerging as a cytokine-like immune regulator that has complex effects in both overnutrition and in the inflammatory response in malnutrition. Because the immune system is immature at birth, malnutrition in childhood might have long-term effects on health.

400 citations


Journal ArticleDOI
Abstract: Lack of adequate macronutrients or selected micronutrients, especially zinc, selenium, iron, and the antioxidant vitamins, can lead to clinically significant immune deficiency and infections in children. Undernutrition in critical periods of gestation and neonatal maturation and during weaning impairs the development and differentiation of a normal immune system. Infections are both more frequent and more often become chronic in the malnourished child. Recent identification of genetic mechanisms is revealing critical pathways in the gastrointestinal immune response. New studies show that the development of tolerance, control of inflammation, and response to normal mucosal flora are interrelated and linked to specific immune mechanisms. Nutrients act as antioxidants and as cofactors at the level of cytokine regulation. Protein calorie malnutrition and zinc deficiency activate the hypothalamic-pituitary-adrenal axis. Increased circulating levels of glucocorticoids cause thymic atrophy and affect hematopoiesis. Chronic undernutrition and micronutrient deficiency compromise cytokine response and affect immune cell trafficking. The combination of chronic undernutrition and infection further weakens the immune response, leading to altered immune cell populations and a generalized increase in inflammatory mediators. Obesity caused by excess nutrition or excess storage of fats relative to energy expenditure is a form of malnutrition that is increasingly seen in children. Leptin is emerging as a cytokine-like immune regulator that has complex effects in both overnutrition and in the inflammatory response in malnutrition. Because the immune system is immature at birth, malnutrition in childhood might have long-term effects on health.

376 citations


Journal ArticleDOI
TL;DR: To the best of the knowledge, this is the first report of a specific nutritional deficiency driving changes in a viral genome, permitting an avirulent virus to acquire virulence due to genetic mutation.
Abstract: Previous work from our laboratory demonstrated that selenium deficiency in the mouse allows a normally benign (amyocarditic) cloned and sequenced Coxackievirus to cause significant heart damage. Furthermore, Coxsackievirus recovered from the hearts of selenium-deficient mice inoculated into selenium-adequate mice still induced significant heart damage, suggesting that the amyocarditic Coxsackievirus had mutated to a virulent phenotype. Here we report that sequence analysis revealed six nucleotide changes between the virulent virus recovered from the selenium-deficient host and the avirulent input virus. These nucleotide changes are consistent with known differences in base composition between virulent and avirulent strains of Coxsackievirus. To the best of our knowledge, this is the first report of a specific nutritional deficiency driving changes in a viral genome, permitting an avirulent virus to acquire virulence due to genetic mutation.

350 citations


Journal ArticleDOI
TL;DR: A role for endogenously expressed Trp1 in regulating a Ca2-selective current activated upon Ca2+ store depletion is supported.
Abstract: SPECIFIC AIMTo determine whether host selenium (Se) deficiency can induce changes in the genome of a replicating influenza virus such that a normally mild virus converts into a more virulent strain and to characterize such genomic changes.PRINCIPAL FINDINGS1. Replication of a mild strain of influenza virus in Se-deficient mice results in a novel virulent strain that causes severe lung pathology even when passed into Se-adequate miceSe-deficient mice developed much more severe lung pathology postinfection with influenza virus than Se-adequate infected mice. To determine whether host factors or viral factors were responsible for the increased pathogenicity of influenza virus that had replicated in Se-deficient mice, a passage experiment was performed. We infected groups of Se-adequate and Se-deficient mice with influenza A/Bangkok/1/79 (H3N2). At 5 days postinfection, the mice were killed and virus was recovered from the lungs. Five separate isolates from each group of mice were used to inoculate five indiv...

245 citations


Journal ArticleDOI
TL;DR: TNF-α showed strong antiviral activity against avian, swine, and human influenza viruses, and the antiviral effect of TNF- α was greater than that of gamma or alpha interferon.
Abstract: Previous studies have associated influenza virus-induced expression of inflammatory cytokines, including tumor necrosis factor alpha (TNF-α), with influenza pathogenesis in the human respiratory tract and have suggested that alpha and beta interferons are the first cytokines recruited to counteract such infection. However, we report here that TNF-α has powerful anti-influenza virus activity. When infected with influenza virus, cultured porcine lung epithelial cells expressed TNF-α in a dose-dependent manner. Expression of TNF-α was induced only by replicating virus. TNF-α showed strong antiviral activity against avian, swine, and human influenza viruses, and the antiviral effect of TNF-α was greater than that of gamma or alpha interferon. These findings suggest that TNF-α serves as the first line of defense against influenza virus infection in the natural host.

201 citations


"Protection from H1N1 influenza viru..." refers background in this paper

  • ...In particular, TNF-α has been reported to exert an anti-influenza virus effect [22]....

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