Polonis V R, Anderson G R, Vahey M T, Morrow P J, Stoler D, Redfield R R
Department of Retroviral Research, Walter Reed Army Institute of Research, Rockville, Maryland 20850.
J Biol Chem. 1991 Jun 25;266(18):11421-4.
The effects of oxygen deprivation, or anoxia, on human immunodeficiency virus (HIV-1) expression in chronically (ACH.2) and acutely (H9/HIV-1-IIIB) infected cell lines was investigated. Temporary cellular anoxia has previously been shown to activate transcription of endogenous type C leukemia virus sequences, resulting in a significant increase in retroviral RNA within the cell (1). Here we report a 15-fold increase in HIV-1-specific RNA in unstimulated ACH.2 T cells within 24 h of anoxia. This induction of RNA is accompanied by an accumulation of intracellular p24 gag protein as well as an increase in envelope protein. Anoxia induces a further increase in total HIV-1 RNA in ACH.2 cells prestimulated to produce virus by phorbol 12-myristate 13-acetate and in H9 T cells acutely infected with HIV-1-IIIB. The induction of RNA in ACH.2 cells appears to be reversible. Anoxic culture for 24 h followed by a 24-h re-oxygenation period results in a return to "resting state" levels of HIV-1 RNA. These data indicate that oxygen tension within the cellular environment modulates HIV-1 expression, providing a model system in which to study the reversible regulation of HIV-1 RNA and viral gene products within the cell.
研究了缺氧（即无氧）对慢性感染（ACH.2）和急性感染（H9/HIV-1-IIIB）细胞系中人类免疫缺陷病毒（HIV-1）表达的影响。先前已表明，短暂的细胞缺氧可激活内源性C型白血病病毒序列的转录，导致细胞内逆转录病毒RNA显著增加（1）。在此，我们报告缺氧24小时内，未受刺激的ACH.2 T细胞中HIV-1特异性RNA增加了15倍。这种RNA的诱导伴随着细胞内p24 gag蛋白的积累以及包膜蛋白的增加。缺氧会使预先用佛波醇12-肉豆蔻酸酯13-乙酸酯刺激以产生病毒的ACH.2细胞以及急性感染HIV-1-IIIB的H9 T细胞中的总HIV-1 RNA进一步增加。ACH.2细胞中RNA的诱导似乎是可逆的。缺氧培养24小时后再进行24小时的复氧期，会使HIV-1 RNA恢复到“静止状态”水平。这些数据表明，细胞环境中的氧张力调节HIV-1表达，提供了一个研究细胞内HIV-1 RNA和病毒基因产物可逆调节的模型系统。
