Pohlmyer Christopher W, Bullen C Korin, Martin Alyssa R, Laird Gregory M, Chioma Stanley U, Walker-Sperling Victoria E K, Blankson Joel N
Center for AIDS Research, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD.
Yale J Biol Med. 2017 Jun 23;90(2):331-336. eCollection 2017 Jun.
Elite Controllers or Suppressors (ES) are patients who control HIV replication without antiretroviral therapy. In this study, we compared baseline and inducible HIV-1 mRNA levels in CD4+ T cells from ES and chronic progressors (CPs) receiving suppressive antiretroviral therapy. We quantified basal levels of cell associated HIV-1 mRNA in CD4+ T cells isolated from CPs and ES. Additionally, we measured the fold upregulation of intracellular HIV-mRNA after stimulation of CD4+ T cells with phorbol 12-myristate 13-acetate (PMA) and ionomycin, and quantified the amount of HIV-mRNA levels released into culture supernatant. ES have significantly less cell associated HIV-mRNA per 5x10 cells (p = 0.003); 8 of 10 CPs had quantifiable HIV-1 mRNA at baseline, whereas this was present in only 2 of 10 ES. Upon stimulation with PMA and ionomycin, 4 of 5 CPs and 7 of 9 ES showed increased cell associated HIV-mRNA. Interestingly, released HIV-1 mRNA could be detected in supernatants of CD4+ T cells stimulated with PMA/ionomycin from 5 of 8 ES. Our results demonstrate that while the baseline levels of cell associated HIV-1 mRNA are significantly lower in ES compared to CPs, stimulation of CD4+ T cells results in a comparable relative upregulation of viral transcription.
精英控制者或抑制者(ES)是指在未接受抗逆转录病毒治疗的情况下控制HIV复制的患者。在本研究中,我们比较了接受抑制性抗逆转录病毒治疗的ES和慢性进展者(CP)的CD4 + T细胞中HIV-1 mRNA的基线水平和诱导水平。我们对从CP和ES中分离出的CD4 + T细胞中与细胞相关的HIV-1 mRNA的基础水平进行了定量。此外,我们在用佛波醇12-肉豆蔻酸酯13-乙酸酯(PMA)和离子霉素刺激CD4 + T细胞后测量了细胞内HIV-mRNA的上调倍数,并对释放到培养上清液中的HIV-mRNA水平进行了定量。每5×10个细胞中,ES的细胞相关HIV-mRNA明显较少(p = 0.003);10名CP中有8名在基线时具有可量化的HIV-1 mRNA,而10名ES中只有2名存在这种情况。在用PMA和离子霉素刺激后,5名CP中的4名和9名ES中的7名显示细胞相关HIV-mRNA增加。有趣的是,在8名ES中,有5名在用PMA/离子霉素刺激的CD4 + T细胞上清液中可检测到释放的HIV-1 mRNA。我们的结果表明,虽然与CP相比,ES中细胞相关HIV-1 mRNA的基线水平显著较低,但CD4 + T细胞的刺激导致病毒转录的相对上调相当。