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Journal of Virology, October 2003, p. 10304-10313, Vol. 77, No. 19
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.19.10304-10313.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

The Vpu Protein of Human Immunodeficiency Virus Type 1 Plays a Protective Role against Virus-Induced Apoptosis in Primary CD4⁺ T Lymphocytes

Department of Virology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871,¹ Department of Virology and Parasitology, School of Medicine, Fujita Health University, Toyoake, Aichi 470-1192, Japan²

Received 15 April 2003/ Accepted 2 July 2003

Previous data revealed that primary cultures of peripheral blood mononuclear cells (PBMCs) were killed by apoptosis at higher rates after infection with two CRF01_AE primary isolates of human immunodeficiency virus type 1 (HIV-1) than after infection with five other CRF01_AE primary isolates, five subtype B primary isolates, and two subtype B laboratory strains. Here, we show evidence that mutations at the vpu gene which were exclusively identified only in the two CRF01_AE isolates mentioned above are involved in their abilities to induce massive apoptosis in primary CD4⁺ T lymphocytes. The rates of virus production by these two isolates in the culture media of infected PBMCs were lower (the same as those of the other CRF01_AE isolates) than those of the subtype B isolates. To confirm the correlation between the higher apoptosis-inducing abilities and the mutations at the vpu gene, infectious molecular clone pNL4-3-based vpu mutants were constructed and examined for their apoptosis induction levels. The apoptosis induction levels after introduction of the vpu mutations were greatly increased in primary CD4⁺ T lymphocytes. In contrast, the apoptosis induction abilities of these vpu mutants were lower in human T-cell line MT-4. Thus, the Vpu protein of HIV-1 could play a protective role against virus-induced apoptosis in primary CD4⁺ T lymphocytes.