The vpu protein of human immunodeficiency virus type 1 plays a protective role against virus-induced apoptosis in primary CD4(+) T lymphocytes.
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.
Komoto
Satoshi
S
Department of Virology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan.
Tsuji
Shoutaro
S
Ibrahim
Madiha S
MS
Li
Yong-Gang
YG
Warachit
Jiranan
J
Taniguchi
Koki
K
Ikuta
Kazuyoshi
K
D000595:Amino Acid Sequence; D017209:Apoptosis; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology*; D002478:Cells, Cultured; D015497:HIV-1 / Q000502:physiology*; D054298:Human Immunodeficiency Virus Proteins; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D054334:Viral Regulatory and Accessory Proteins / Q000502:physiology*; D014779:Virus Replication; D000086082:Viroporin Proteins
D054298:Human Immunodeficiency Virus Proteins; D054334:Viral Regulatory and Accessory Proteins; C514859:vpu protein, Human immunodeficiency virus 1; D000086082:Viroporin Proteins