Rhesus monkey simian immunodeficiency virus infection as a model for assessing the role of selenium in AIDS.
The objective of this study was to determine whether simian immunodeficiency virus (SIV) infection of 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 75Se, 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 Sep15 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.
Xu
Xue-Ming
XM
Section on the Molecular Biology of Selenium, Basic Research Laboratory, National Cancer Institute/NIH, Building 37, Room 2D09, Bethesda, MD 20892, USA.
Carlson
Bradley A
BA
Grimm
Tobias A
TA
Kutza
Joseph
J
Berry
Marla J
MJ
Arreola
Raul
R
Fields
Karen H
KH
Shanmugam
Ilanchezhian
I
Jeang
Kuan-Teh
KT
Oroszlan
Stephen
S
Combs
Gerald F
GF
Marx
Preston A
PA
Gladyshev
Vadim N
VN
Clouse
Kathleen A
KA
Hatfield
Dolph L
DL
D000163:Acquired Immunodeficiency Syndrome / Q000097:blood*; D000818:Animals; D002460:Cell Line; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D005786:Gene Expression Regulation; D015696:Gene Products, tat / Q000235:genetics / Q000378:metabolism; D006678:HIV / Q000502:physiology; D006801:Humans; D019169:Jurkat Cells; D008253:Macaca mulatta / Q000097:blood* / Q000821:virology*; D011485:Protein Binding; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D012343:RNA, Transfer / Q000032:analysis / Q000235:genetics; D012643:Selenium / Q000097:blood*; D012644:Selenium Radioisotopes / Q000378:metabolism; D051140:Selenoproteins; D016097:Simian Acquired Immunodeficiency Syndrome / Q000097:blood*; D015302:Simian Immunodeficiency Virus / Q000502:physiology; D054322:tat Gene Products, Human Immunodeficiency Virus
D015696:Gene Products, tat; D011506:Proteins; C495238:SELENOF protein, human; D012644:Selenium Radioisotopes; D051140:Selenoproteins; D054322:tat Gene Products, Human Immunodeficiency Virus; D012343:RNA, Transfer; D012643:Selenium