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Rhesus monkey simian immunodeficiency virus infection as a model for assessing the role of selenium in AIDS

  1. Author:
    Xu, X. M.
    Carlson, B. A.
    Grimm, T. A.
    Kutza, J.
    Berry, M. J.
    Arreola, R.
    Fields, K. H.
    Shanmugam, I.
    Jeang, K. T.
    Oroszlan, S.
    Combs, G. F.
    Marx, P. A.
    Gladyshev, V. N.
    Clouse, K. A.
    Hatfield, D. L.

  2. Author Address

    NCI, Sect Mol Biol Selenium, Basic Res Lab, NIH, Bldg 37,Room 2D09, Bethesda, MD 20892 USA NCI, Sect Mol Biol Selenium, Basic Res Lab, NIH, Bethesda, MD 20892 USA US FDA, Ctr Biol Evaluat & Res, Div Monoclonal Antibodies, Rockville, MD 20857 USA Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Thyroid, Boston, MA 02115 USA NIAID, Mol Virol Sect, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA NCI, HIV Drug Resistance Program, Ctr Canc Res, Frederick, MD 21701 USA Cornell Univ, Div Nutr Sci, Dept Nutr, Ithaca, NY 14853 USA Tulane Univ, Hlth Sci Ctr, Sch Publ Hlth & Trop Med, Covington, LA USA Tulane Natl Primate Res Ctr, Covington, LA USA Univ Nebraska, Dept Biochem, Lincoln, NE 68583 USA Hatfield DL NCI, Sect Mol Biol Selenium, Basic Res Lab, NIH, Bldg 37,Room 2D09, Bethesda, MD 20892 USA
    1. Year: 2002
  2. Journal: Jaids-Journal of Acquired Immune Deficiency Syndromes
    1. 31
    2. 5
    3. Pages: 453-463
  4. Type of Article: Article
  1. Abstract:

    The objective of this study was to determine whether simian immunodeficiency virus (SIV) infection of rhesus macaques could be used as a model system to assess the role of selenium in AIDS. Plasma and serum selenium levels were determined by standard assays in monkeys before and after inoculation of SIV. SIV-infected cells or cells expressing the HIV Tat protein were labeled with Se-75, and protein extracts were prepared and electrophoresed to analyze selenoprotein expression. Total tRNA was isolated from CEMx174 cells infected with SIV or from KK1 cells infected with HIV, and selenocysteine tRNA isoforms were characterized by reverse phase chromatography. SIV-infected monkeys show a decrease in blood selenium levels similar to that observed in AIDS with development of SAIDS. Cells infected with SIV in vitro exhibit reduced selenoprotein levels and an accumulation of small molecular weight selenium compounds relative to uninfected cells. Examination of the selenocysteine tRNA isoforms in HIV-infected KK1 cells or SIV-infected CEMx174 cells reveals an isoform distribution characteristic of selenium-deficient cells. Furthermore, transfection of Jurkat E6 cells with the Tat gene selectively altered selenoprotein synthesis, with GPX4 and Sep 15 being the most inhibited and TR1 the most enhanced. Taken together, the data show that monkeys infected with SIV in vivo and cells infected with SIV in vitro will provide appropriate models for investigating the mechanism(s) responsible for reduced selenium levels that accompany the progression of AIDS in HIV disease.

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