12th International AIDS Conference Geneva, Switzerland - June 28-July 3, 1998

Int Conf AIDS 1998 Jun 28-Jul 3; 12:10 (abstract no. 11142)

Iwakura Y, Maiyao T
Institute of Medical, Tokyo Minatoku Shirokanede, Japan.

OBJECTIVES: To examine the role of a HIV-1 accessory protein, Vpr, on viral replication in vivo and AIDS pathogenesis, we generated transgenic mice carrying the vpr gene.

METHODS: We produced transgenic mice expressing HIV-1 (NL4-3-2 strain) vpr under the control of the mouse CD4 promoter/enhancer. To examine whether Vpr has any effects on T-cell subsets in vivo, FACS analyses was performed on cells from the thymus and peripheral lymphoid organs of Vpr-transgenic mice. Cell cycle analysis and detection of apoptotic cells in transgenic thymocytes were carried out either by propidium iodide (PI) or by Annexin V staining, respectively.

RESULTS: In the thymus of Vpr transgenic mice, high levels of mRNA expression from the transgene and thymic atrophy were observed. FACS analyses showed decrease of CD4/CD8 double positive cells and increase of CD4/CD8 negative cells in the thymus and decrease of T cells in peripheral lymphoid organs. Although previous studies suggested that Vpr induces G2 arrest of the cell cycle, this was not observed in Vpr transgenic thymocytes. In contrast, significant increase of apoptotic cells was observed in the transgenic thymus.

CONCLUSION: We found that Vpr induces apoptosis of thymocytes in Vpr transgenic mice causing thymic atrophy and T cell depletion in peripheral lymphatic organs. These results suggest that Vpr play an important role in the CD4 positive T cell depletion observed in AIDS patients.

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