T Cell Apoptosis Causes Peripheral T Cell Depletion in Mice Transgenic for the HIV-1 vpr Gene

• Published in: Virology (New York, N.Y.) Vol. 285; no. 2; pp. 181 - 192
• Main Authors: Yasuda, Jiro, Miyao, Tamaki, Kamata, Masakazu, Aida, Yoko, Iwakura, Yoichiro
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 05.07.2001
• Subjects: Animals; Apoptosis; Bax protein; bcl-2-Associated X Protein; Bcl-x protein; Cell Survival; Fas antigen; Fas Ligand Protein; fas Receptor - genetics; fas Receptor - metabolism; FasL protein; Gene Expression; Gene Products, vpr - genetics; Gene Products, vpr - immunology; HIV-1 - immunology; HIV-1 - pathogenicity; human immunodeficiency virus 1; Humans; Lymphocyte Depletion; Membrane Glycoproteins - metabolism; Mice; Mice, Transgenic; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins c-bcl-2 - genetics; T-Lymphocytes - cytology; T-Lymphocytes - immunology; Thymus Gland - cytology; vpr gene; vpr Gene Products, Human Immunodeficiency Virus
• ISSN: 0042-6822; 1096-0341
• DOI: 10.1006/viro.2001.0964

Vpr, an accessory protein of HIV, is known to affect viral replication as well as cell growth, differentiation, and apoptosis in vitro. To investigate its pathogenicity in vivo, we have produced mice transgenic for the HIV-1 vpr gene with the CD4 enhancer/promoter. Interestingly, apoptotic death of T lymphocytes was enhanced in those mice, causing marked reduction of T cells in lymphatic organs and peripheral blood. Involvement of Bcl-x, Bax, and Caspase-1, but not of the Fas–Fas ligand system, was suggested in the apoptotic processes. These observations suggest that Vpr is involved in the pathogenesis of T cell depletion in HIV-infected people.