CXCR4 tropic human immunodeficiency virus type 1 induces an apoptotic cascade in immature infected thymocytes that resembles thymocyte negative selection.

Abstract

HIV-1 often replicates in the thymus of infected individuals, causing thymocyte depletion and thymic dysfunction. Nevertheless, the mechanisms by which thymocyte depletion occurs are not clear. Here we report that HIV-1 infection induced apoptosis primarily in productively infected thymocytes; aldrithiol-2 or Efavirenz treatment largely abrogated HIV-1-induced apoptosis. Moreover, X4-HIV-1 induced apoptosis primarily in immature CD4+ CD8+ (DP) thymocytes whereas most mature CD4 or CD8 single-positive (SP) thymocytes were resistant to X4 HIV-1-induced apoptosis despite infection. Consistent with this, we observed significant induction of several genes involved in negative selection of DP thymocytes. Furthermore, treatment of thymocytes with cycloheximide abrogated HIV-1-induced apoptosis, implying a requirement for de novo protein synthesis. Our results suggest that HIV-1-induced apoptosis of thymocytes requires the activation of caspases and the participation of mitochondrial apoptosis effectors, which serve to amplify the apoptotic signal, a process similar to that elaborated during thymocyte negative selection.

• Authors: Shailesh K Choudhary, Russell M Walker, Douglas M Powell, Vicente Planelles, Craig Walsh, David Camerini
• Journal: Virology (Virology) Vol. 352 Issue 2 Pg. 268-84 (Sep 01 2006) ISSN: 0042-6822 [Print] United States
• PMID: 16777169 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• CD4 Antigens
• CD8 Antigens
• Flavonoids
• Receptors, CXCR4
• Cyclosporine
• Caspases
• 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one

Topics

• Apoptosis (genetics, immunology, physiology)
• CD4 Antigens (metabolism)
• CD8 Antigens (metabolism)
• Caspases (metabolism)
• Cell Differentiation
• Cyclosporine (pharmacology)
• Flavonoids (pharmacology)
• Gene Expression
• HIV Infections (genetics, immunology, pathology, virology)
• HIV-1 (pathogenicity, physiology)
• Humans
• In Vitro Techniques
• Protein Biosynthesis
• Receptors, CXCR4 (physiology)
• T-Lymphocytes (drug effects, immunology, pathology, virology)
• Virus Replication