1. Mechanisms associated with thymocyte apoptosis induced by simian immunodeficiency virus
- Author
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Amy Forand-Barabasz, R. Paul Johnson, Michelle Connole, Andrew A. Lackner, Michael L. Rosenzweig, and Marie-Pier Tremblay
- Subjects
Fas Ligand Protein ,T-Lymphocytes ,Immunology ,Cell ,Simian Acquired Immunodeficiency Syndrome ,Down-Regulation ,Viremia ,Apoptosis ,Thymus Gland ,medicine.disease_cause ,Ligands ,Lymphocyte Depletion ,Immunophenotyping ,MHC class I ,medicine ,Immunology and Allergy ,Animals ,fas Receptor ,Membrane Glycoproteins ,biology ,Histocompatibility Antigens Class I ,virus diseases ,Cell Differentiation ,Simian immunodeficiency virus ,medicine.disease ,Macaca mulatta ,Thymic Tissue ,medicine.anatomical_structure ,Viral replication ,Animals, Newborn ,Proto-Oncogene Proteins c-bcl-2 ,Acute Disease ,biology.protein ,Simian Immunodeficiency Virus ,CD8 - Abstract
Despite considerable research, the mechanisms by which HIV disrupts thymic function remain controversial. We have described the phenotypic changes that occur in the thymus of SIV-infected macaques during acute SIV infection. In this study, we analyzed the effects of SIV infection on apoptotic pathways in thymic tissue from newborn macaques infected with SIV. Thymocyte apoptosis was accompanied by a modest increase in surface Fas expression, a profound decrease in the frequency of bcl-2-positive cells, as well as the amount of bcl-2 per cell. With control of viral replication, levels of bcl-2 and Fas returned to baseline together with a return to basal levels of apoptosis. In the thymus, SIV infection resulted in depletion of CD4+CD8+ thymocytes, an increase in apoptosis of thymocytes, and a down-regulation of MHC class I molecules. These changes peaked 14–21 days after infection at or just after peak viremia. This data further suggests disruption of the antiapoptotic pathway regulated by bcl-2 plays a critical role in SIV-induced apoptosis of thymocytes.
- Published
- 2000