Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institutet, Huddinge, Stockholm, Sweden.
Science for Life Laboratory, Division of Proteomics and Nanobiotechnology, KTH Royal Institute of Technology, Solna, Stockholm, Sweden.
Sci Rep. 2017 Apr 6;7(1):666. doi: 10.1038/s41598-017-00759-8.
A major challenge in evaluating the success of HIV eradication approaches is the need for accurate measurement of persistent HIV during effective antiretroviral therapy (ART). Previous studies have reported that the anti-HIV antibody assay "luciferase immuno-precipitation systems (LIPS)" can distinguish HIV-infected individuals harboring different sizes of the viral reservoirs. We performed antibody profiling of HIV-1 proteomes using LIPS in viremic progressors (n = 38), elite controllers (ECs; n = 19) and patients with fully suppressive long-term antiretroviral therapy (ART) (n = 19) (mean 17 years). IgG was quantified against six HIV-1 fusion proteins: p24, gp41, RT, Tat, integrase and protease. Lower antibody levels to all six-fusion proteins were observed in long-term ART patients compared to viremics (p < 0.05). In contrast ECs had lower antibody levels only against Tat and Integrase (p < 0.05). Principal component analysis and cluster-network analysis identified that 68% (13/19) of the long-term ART patients clustered together with 26% (5/19) ECs. The remaining ECs clustered together with the viremics indicating non-homogeneity among the ECs. The low anti-HIV levels in the long-term treated patients may indicate a restricted remaining viral replication. In contrast, the higher levels in ECs suggest a continuous viral expression with a limited concomitant release of extracellular virus.
评估 HIV 根除方法成功的主要挑战是需要准确测量有效的抗逆转录病毒治疗 (ART) 期间持续存在的 HIV。以前的研究报告称,抗 HIV 抗体检测“荧光素酶免疫沉淀系统 (LIPS)”可以区分携带不同大小病毒库的 HIV 感染个体。我们使用 LIPS 在病毒血症进展者 (n = 38)、精英控制者 (EC; n = 19) 和接受长期完全抑制性抗逆转录病毒治疗 (ART) 的患者 (n = 19) (平均 17 年) 中对 HIV-1 蛋白质组进行了抗体分析。针对六种 HIV-1 融合蛋白:p24、gp41、RT、Tat、整合酶和蛋白酶,对 IgG 进行了定量。与病毒血症患者相比,长期接受 ART 的患者对所有六种融合蛋白的抗体水平较低 (p < 0.05)。相比之下,EC 仅对 Tat 和整合酶的抗体水平较低 (p < 0.05)。主成分分析和聚类网络分析确定,68% (13/19) 的长期接受 ART 的患者与 26% (5/19) 的 EC 一起聚类。其余的 EC 与病毒血症患者聚类在一起,表明 EC 之间存在非均质性。长期接受治疗的患者中的低 HIV 水平可能表明剩余的病毒复制受到限制。相比之下,EC 中的高水平表明持续的病毒表达伴随着有限的细胞外病毒释放。