HCV viraemia associates with NK cell activation and dysfunction in antiretroviral therapy-treated HIV/HCV-co-infected subjects.
HCV viraemia associates with NK cell activation and dysfunction in antiretroviral therapy-treated HIV/HCV-co-infected subjects.
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DOI：
10.1111/jvh.12714
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发表时间：
2017-10
影响因子：
2.5
通讯作者：
Montaner LJ
中科院分区：
文献类型：
--
作者：
Papasavvas E;Azzoni L;Yin X;Liu Q;Joseph J;Mackiewicz A;Ross B;Lynn KM;Jacobson JM;Mounzer K;Kostman JR;Montaner LJ
与接受抗逆转录病毒治疗（ART）的HIV/HCV合并感染相比，丙型肝炎病毒（HCV） RNA水平对慢性HCV单感染者免疫状态的影响尚不清楚。研究了78例接受HCV治疗的非裔美国人HCV病毒血症/naïve（33例HCV基因型1单感染者，45例HCV基因型1/HIV合并ART感染）。进行临床和肝酶测定。流式细胞术分析全血免疫亚群变化。利用外周血单个核细胞（PBMC）进行当日组成型和体外干扰素(IFN) α诱导的信号转导和转录激活因子（STAT）磷酸化、K562靶细胞裂解和K562靶细胞识别介导的IFN-γ产生。采用R（2.5.1）或JMP Pro 11进行统计学分析。虽然两组在肝酶水平上没有差异，但与HCV相比，HIV/HCV具有更高的T细胞激活/衰竭和组成性STAT-1磷酸化。相比之下，CD4+FoxP3+CD25+频率、NK细胞上IFN-αR的表达以及IFN-α-诱导的直接细胞毒性在HIV/HCV中较低。线性回归模型进一步支持了这些结果。最后，HCV病毒载量（vl）和CD4+ T细胞计数的增加在两组之间分别对NK细胞活性和T细胞活性产生相反的影响。抗逆转录病毒治疗的HIV/HCV合并感染的HCV病毒血症与HCV单感染的HCV病毒载量相比，更大的免疫激活/衰竭和NK功能障碍相关。在接受抗逆转录病毒治疗的HIV合并感染/未治疗的HCV病毒血症患者中发现的更明显的免疫调节可能影响HCV疾病进展和/或对免疫治疗的反应。
The impact of Hepatitis C virus (HCV) RNA levels on immune status in chronically HCV mono-infected when compared to HIV/HCV co-infected on antiretroviral therapy (ART) remains poorly understood. A total of 78 African American subjects HCV viremic/naïve to HCV treatment (33 HCV genotype 1 mono-infected, 45 HCV genotype 1/HIV co-infected on ART) were studied. Clinical and liver enzymes measurements were performed. Whole blood was analyzed for immune subset changes by flow-cytometry. Peripheral blood mononuclear cells (PBMC) were used for same-day constitutive and in vitro Interferon (IFN)-α-induced Signal Transducer and Activator of Transcription (STAT) phosphorylation, K562 target cell lysis and K562 target cell recognition-mediated IFN-γ production. Statistical analysis was done using R (2.5.1) or JMP Pro 11. While both groups did not differ in the level of liver enzymes, HIV/HCV had higher T cell activation/exhaustion, and constitutive STAT-1 phosphorylation compared to HCV. In contrast, CD4+FoxP3+CD25+ frequency, IFN-αR expression on NK cells, as well as constitutive and IFN-α-induced direct cytotoxicity were lower in HIV/HCV. Linear regression models further supported these results. Finally, increase in HCV viral load (vl) and CD4+ T cell count had an opposite effect between the two groups on NK cell activity, and T cell activation respectively. HCV viraemia in antiretroviral -treated HIV/HCV co-infection was associated with greater immune activation/exhaustion and NK dysfunction than HCV viral load alone in HCV mono-infection. The more pronounced immune modulation noted in antiretroviral treated HIV co-infected / untreated HCV viremic subjects may impact HCV disease progression and/or response to immunotherapy.
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影响因子：
15.3
作者：
Crotta, Stefania;Stilla, Annalisa;Wack, Andreas;D'Andrea, Annalisa;Nuti, Sandra;D'Oro, Ugo;Mosca, Marta;Filliponi, Franco;Brunetto, R Maurizia;Bonino, Ferruccio;Abrignani, Sergio;Valiante, Nicholas M
通讯作者：
Valiante, Nicholas M
影响因子：
6.4
作者：
Collin M;McGovern N;Haniffa M
通讯作者：
Haniffa M
影响因子：
3.8
作者：
Azzoni, Livio;Chehimi, Jihed;Montaner, Luis J.
通讯作者：
Montaner, Luis J.
影响因子：
25.7
作者：
Deignan, T;Curry, MP;O'Farrelly, C
通讯作者：
O'Farrelly, C
影响因子：
4.4
作者：
Anthony, DD;Yonkers, NL;Valdez, H
通讯作者：
Valdez, H