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携带 ALV-J gag/env 的外泌体对免疫细胞具有负向作用。

Exosomes carring gag/env of ALV-J possess negative effect on immunocytes.

机构信息

College of Veterinary Medicine, Shandong Agricultural University, Tai'an, PR China; Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Shandong Agricultural University, Tai'an, PR China.

College of Veterinary Medicine, Shandong Agricultural University, Tai'an, PR China.

出版信息

Microb Pathog. 2017 Nov;112:142-147. doi: 10.1016/j.micpath.2017.09.013. Epub 2017 Sep 12.

DOI:10.1016/j.micpath.2017.09.013
PMID:28916320
Abstract

J subgroup avian leukosis virus (ALV-J) is an exogenous retrovirus of avian. A key feature of ALV-J infection is leading to severe immunosuppressive characteristic of diseases. Viral components of retrovirus were reported closely associated with immunosuppression, and several similarities between exosomes and retrovirus preparations have lead to the hypotheses of retrovirus hijacker exosomes pathway. In this study, we purified exosomes from DF-1 cells infected and uninfected by ALV-J. Electron microscopy and mass spectrometry (MS) analysis showed that ALV-J not only increased the production of exosomes from ALV-J infected DF-1 cells (Exo-J) but also stimulated some proteins expression, especially ALV-J components secreted in exosomes. Immunosuppressive domain peptide (ISD) of envelope subunit transmembrane (TM) and gag of ALV-J were secreted in Exo-J. It has been reported that HIV gag was budded from endosome-like domains of the T cell plasma membrane. But env protein was first detected in exosomes from retrovirus infected cells. We found that Exo-J caused negative effects on splenocytes in a dose-dependant manner by flow cytometric analysis. And low dose of Exo-J activated immune activity of splenocytes, while high dose possessed immunosuppressive properties. Interestingly, Exo-J has no significant effects on the immunosuppression induced by ALV-J, and the immunosuppressive effects induced by Exo-J lower than that by ALV-J. Taken together, our data indicated that Exo-J supplied a microenvironment for the replication and transformation of ALV-J.

摘要

J 亚群禽白血病病毒(ALV-J)是一种禽类的外源性逆转录病毒。ALV-J 感染的一个关键特征是导致疾病严重的免疫抑制特征。逆转录病毒的病毒成分被报道与免疫抑制密切相关,并且外泌体和逆转录病毒制剂之间的几个相似性导致了逆转录病毒劫持外泌体途径的假说。在这项研究中,我们从感染和未感染 ALV-J 的 DF-1 细胞中纯化了外泌体。电子显微镜和质谱(MS)分析表明,ALV-J 不仅增加了感染 ALV-J 的 DF-1 细胞(Exo-J)中外泌体的产生,而且还刺激了一些蛋白质的表达,特别是 ALV-J 成分在 Exo-J 中分泌。ALV-J 的 envelope 亚单位跨膜(TM)和 gag 的免疫抑制域肽(ISD)被分泌到 Exo-J 中。据报道,HIV gag 从 T 细胞质膜的内体样结构域出芽。但是 env 蛋白首先在感染逆转录病毒的细胞中外泌体中被检测到。我们通过流式细胞术分析发现,Exo-J 以剂量依赖的方式对脾细胞产生负面影响。低剂量的 Exo-J 激活了脾细胞的免疫活性,而高剂量则具有免疫抑制特性。有趣的是,Exo-J 对 ALV-J 诱导的免疫抑制没有显著影响,并且 Exo-J 诱导的免疫抑制作用低于 ALV-J。总之,我们的数据表明 Exo-J 为 ALV-J 的复制和转化提供了一个微环境。

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