Jafarian Mahdokht, Mozhgani Sayed-Hamidreza, Patrad Elham, Vaziri Hamidreza, Rezaee Seyed Abdolrahim, Akbarin Mohammad Mehdi, Norouzi Mehdi
Department of Genetics, University of Guilan, University Campus 2, Rasht, Iran.
Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.
Arch Virol. 2017 Apr;162(4):1009-1015. doi: 10.1007/s00705-016-3213-0. Epub 2017 Jan 21.
The main aim of this study was to evaluate the expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and inducible nitric oxide synthase (iNOS) as host factors, and proviral load as the viral parameter, in adult T-cell leukemia/lymphoma (ATLL) individuals and healthy carrier (HC(s)) groups. Peripheral blood mononuclear cells (PBMC) from ATLL patients (n = 17) and HC subjects (as the control group, n = 17) were evaluated using real-time PCR to determine the levels of HTLV-1 proviral load and mRNA expression of ICAM, VCAM-1, and iNOS. ICAM-1 was significantly lower in ATLL patients than in control subjects. Although the expression of VCAM-1 was higher in ATLL individuals, there was no significant difference between the studied groups. In addition, no iNOS expression was found in ATLL patients, when compared to the HCs subjects, while ATLL patients demonstrated a higher level of proviral load when compared to the control group. Considering the importance of ICAM-1 in facilitating immune recognition of infected cells, it is posited that reduction of ICAM-1 expression is a unique strategy for circumventing appropriate immune responses that are mediated by different accessory proteins. Additionally, as the viral regulatory protein Tax and the NF-κB pathway play pivotal roles in expression of iNOS, lack of the latter in ATLL patients may be related to the level of Tax expression, disruption of the NF-κB pathway, or the occurrence of epigenetical mechanisms in the human iNOS promoter. Further studies are recommended to gain a better understanding of the interaction between host and viral factors in HTLV-1 pathogenesis and to identify a possible therapeutic target for ATLL.
本研究的主要目的是评估细胞间黏附分子-1（ICAM-1）、血管细胞黏附分子-1（VCAM-1）和诱导型一氧化氮合酶（iNOS）作为宿主因素的表达情况，以及前病毒载量作为病毒参数，在成人T细胞白血病/淋巴瘤（ATLL）个体和健康携带者（HC）组中的表达。使用实时PCR评估来自ATLL患者（n = 17）和HC受试者（作为对照组，n = 17）的外周血单个核细胞（PBMC），以确定HTLV-1前病毒载量水平以及ICAM、VCAM-1和iNOS的mRNA表达。ATLL患者的ICAM-1显著低于对照组。虽然ATLL个体中VCAM-1的表达较高，但研究组之间无显著差异。此外，与HC受试者相比，ATLL患者未发现iNOS表达，而与对照组相比，ATLL患者的前病毒载量水平更高。考虑到ICAM-1在促进对感染细胞的免疫识别中的重要性，推测ICAM-1表达的降低是规避由不同辅助蛋白介导的适当免疫反应的独特策略。此外，由于病毒调节蛋白Tax和NF-κB途径在iNOS的表达中起关键作用，ATLL患者中iNOS的缺乏可能与Tax表达水平、NF-κB途径的破坏或人iNOS启动子中的表观遗传机制的发生有关。建议进一步研究以更好地了解HTLV-1发病机制中宿主和病毒因素之间的相互作用，并确定ATLL可能的治疗靶点。
