The Vpu protein of human immunodeficiency virus type 1 plays a protective role against virus-induced apoptosis in primary CD4+ T lymphocytes

Satoshi Komoto, Shoutaro Tsuji, Madiha S. Ibrahim, Yong Gang Li, Jiranan Warachit, Koki Taniguchi, Kazuyoshi Ikuta

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Abstract

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 C-RF01_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 pNLA-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.

Original languageEnglish
Pages (from-to)10304-10313
Number of pages10
JournalJournal of Virology
Volume77
Issue number19
DOIs
Publication statusPublished - 01-10-2003

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All Science Journal Classification (ASJC) codes

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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