Premium
Tat Protein Enables HIV Infection of PBMC at Physiological Oxygen Levels
Author(s) -
Sahaf Bita,
Atkuri Kondala,
Heydari Kartoosh,
Rappaport Jay,
Herzenberg Leonard A,
Herzenberg Leonore A
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.2_supplement.508
Subject(s) - peripheral blood mononuclear cell , immune system , apoptosis , biology , immunology , activator (genetics) , programmed cell death , microbiology and biotechnology , virology , in vitro , receptor , genetics
HIV‐1 Trans‐activator of transcription (Tat) protein, an intracellular amplifier of HIV replication, is released in biologically active form. It is known to induce apoptosis in human peripheral blood mononuclear cells (PBMC) cultured under standard conditions in 5% CO 2 incubators in air (21% O 2 ). However, as we show here, it does not induce apoptosis in PBMC cultured at oxygen levels approximating those encountered in vivo , i.e., at 5% (physiologic) O 2 . Under the latter conditions, Tat induces cells to divide and prepares them to be infectable by HIV beginning at two hours rather than the standard PHA/IL‐2 stimulation which takes three days. This observation was missed for many years because PBMC cultured at 21% O 2 die by Activation Induced Cell Death (AICD)! Preliminary data also demonstrate a key phenotypic shift towards memory T cell subset during the 2 h of Tat treatment. These findings suggest a central role for Tat in promoting HIV disease. In essence, Tat released by HIV‐infected cells enables productive infection of neighboring T cells, thereby rapidly spreading infection to produce the viral “storm” that rapidly depletes large numbers of T cells from lymphoid sites early in the disease. In addition, released Tat may foster episodic spread of the infection at sites where immunogens draw infectable T cells into close association with HIV‐infected cells, thereby contributing to the progressive crippling of the immune system in HIV disease.