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

Area of Science:

• Virology
• Immunology
• Nutritional Biochemistry

Background:

• Acquired immunodeficiency syndrome (AIDS) is associated with decreased selenium levels.
• The role of selenium in AIDS pathogenesis remains incompletely understood.
• Simian immunodeficiency virus (SIV) infection in macaques serves as a model for human immunodeficiency virus (HIV) infection.

Purpose of the Study:

• To evaluate simian immunodeficiency virus (SIV) infection in macaques as a model for studying selenium's role in AIDS.
• To analyze changes in selenium levels and selenoprotein expression during SIV infection.
• To investigate the impact of HIV Tat protein on selenoprotein synthesis.

Main Methods:

• Measurement of plasma and serum selenium levels in SIV-infected macaques.
• Analysis of selenoprotein expression in SIV-infected cells and cells expressing HIV Tat protein using 75Se labeling and electrophoresis.
• Characterization of selenocysteine tRNA isoforms in HIV- and SIV-infected cells via reverse phase chromatography.

Main Results:

• SIV-infected macaques exhibited decreased blood selenium levels, similar to AIDS patients.
• SIV-infected cells showed reduced selenoprotein levels and accumulation of small selenium compounds.
• HIV- and SIV-infected cells displayed selenocysteine tRNA isoform distributions indicative of selenium deficiency.
• HIV Tat protein transfection selectively altered selenoprotein synthesis, inhibiting GPX4 and Sep15 while enhancing TR1.

Conclusions:

• SIV infection in macaques is a suitable model for investigating the mechanisms behind selenium depletion in AIDS.
• In vitro SIV infection models also reflect selenium dysregulation seen in HIV disease.
• These models can elucidate the role of selenium in AIDS progression.