Mediouni Sonia, Darque Albert, Baillat Gilbert, Ravaux Isabelle, Dhiver Catherine, Tissot-Dupont Herve, Mokhtari Malika, Moreau Herve, Tamalet Catherine, Brunet Corinne, Paul Pascale, Dignat-George Francoise, Stein Andreas, Brouqui Philippe, Spector Stephen A, Campbell Grant R, Loret Erwann P
University of the Mediterranean, Marseille cedex, France.
Infect Disord Drug Targets. 2012 Feb;12(1):81-6. doi: 10.2174/187152612798994939.
Tat is a viral protein secreted from HIV infected cells and extra cellular Tat is suspected to prevent destruction of HIV infected cells from cells of the cellular immunity. The effect of anti retroviral therapy (ART) on Tat secretion has never been investigated. In this study, we tested for antibody reactivity against Tat variants representative of the main HIV subtypes in HIV positive patients receiving ART with undetectable viral loads ( < 40 copies/mL) over the course of one year with a blood sampling every three months. For each of theses five blood sampling, an average of 50 % of patients had Anti-Tat IgG, it turned out that 86% of patients could recognize Tat at least in one blood sampling during the course of the study. Amazingly, anti-Tat IgG appeared and/or disappeared in 66 % of patients. Only 20% had anti-Tat IgG remaining persistently while 14% were consistently without anti Tat IgG in the five blood sampling. No significant correlation was found between anti-Tat IgG and CD4+ T cell, CD8+ T cell and B cell counts revealing the incapacity of these anti Tat IgG to neutralize extra cellular Tat. Interestingly the absence and then the appearance of anti-Tat IgG in patients suggest the presence of HIV infected cells in the blood that may constitute a significant reservoir of HIV infected cells. As a conclusion antiretroviral therapy does not block the secretion of Tat and may explain why HIV infected cells can survive in spite of an effective ART treatment.
Tat是一种从感染HIV的细胞中分泌的病毒蛋白，细胞外的Tat被怀疑可阻止细胞免疫细胞对感染HIV细胞的破坏。抗逆转录病毒疗法（ART）对Tat分泌的影响从未被研究过。在本研究中，我们检测了接受ART且病毒载量不可检测（<40拷贝/毫升）的HIV阳性患者在一年期间每三个月采血一次时，针对代表主要HIV亚型的Tat变体的抗体反应性。在这五次采血中，平均50%的患者有抗Tat IgG，结果表明86%的患者在研究过程中至少在一次采血中能识别Tat。令人惊讶的是，66%的患者抗Tat IgG出现和/或消失。在五次采血中，只有20%的患者抗Tat IgG持续存在，而14%的患者始终没有抗Tat IgG。未发现抗Tat IgG与CD4 + T细胞、CD8 + T细胞和B细胞计数之间存在显著相关性，这表明这些抗Tat IgG无法中和细胞外的Tat。有趣的是，患者中抗Tat IgG的缺失然后出现表明血液中存在感染HIV的细胞，这些细胞可能构成感染HIV细胞的重要储存库。总之，抗逆转录病毒疗法不会阻断Tat的分泌，这可能解释了为什么尽管进行了有效的ART治疗，感染HIV的细胞仍能存活。
