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系统鉴定宿主免疫关键因素对 SPF 鸡感染 ALV-J 的 PBL 中的病毒感染的影响。

Systematic Identification of Host Immune Key Factors Influencing Viral Infection in PBL of ALV-J Infected SPF Chicken.

机构信息

College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China.

National and Regional Joint Engineering Laboratory for Medicament of Zoonosis Prevention and Control, Guangzhou 510642, China.

出版信息

Viruses. 2020 Jan 16;12(1):114. doi: 10.3390/v12010114.

Abstract

Although research related to avian leukosis virus subgroup J (ALV-J) has lasted for more than a century, the systematic identification of host immune key factors against ALV-J infection has not been reported. In this study, we establish an infection model in which four-week-old SPF chickens are infected with ALV-J strain CHN06, after which the host immune response is detected. We found that the expression of two antiviral interferon-stimulated genes (ISGs) (Mx1 and IFIT5) were increased in ALV-J infected peripheral blood lymphocytes (PBL). A significant CD8 T cell response induced by ALV-J appeared as early as seven days post-infection (DPI), and humoral immunity starting from 21 DPI differed greatly in the time scale of induction level. Meanwhile, the ALV-J viremia was significantly decreased before antibody production at 14 DPI, and eliminated at 21 DPI under a very low antibody level. The up-regulated CD8 T cell in the thymus (14DPI) and PBL (7 DPI and 21 DPI) was detected, indicating that the thymus may provide the output of CD8 T cell to PBL, which was related to virus clearance. Besides, up-regulated chemokine CXCLi1 at 7 DPI in PBL was observed, which may be related to the migration of the CD8 T cell from the thymus to PBL. More importantly, the CD8 T cell response of the CD8αβ phenotype may produce granzyme K, NK lysin, or IFN-γ for clearing viruses. These findings provide novel insights and direction for developing effective ALV-J vaccines.

摘要

虽然有关禽白血病病毒亚群 J(ALV-J)的研究已经持续了一个多世纪,但针对 ALV-J 感染的宿主免疫关键因素的系统鉴定尚未见报道。在本研究中,我们建立了一个感染模型,即将 4 周龄 SPF 鸡用 ALV-J 株 CHN06 感染,然后检测宿主的免疫反应。我们发现,两种抗病毒干扰素刺激基因(ISGs)(Mx1 和 IFIT5)在 ALV-J 感染的外周血淋巴细胞(PBL)中的表达增加。ALV-J 感染后最早在 7 天即可观察到明显的 CD8 T 细胞反应,而从 21 天开始的体液免疫在诱导水平的时间尺度上有很大差异。同时,在产生抗体之前,ALV-J 血症在 14 天显著降低,在抗体水平非常低的情况下在 21 天消除。在胸腺(14 天)和 PBL(7 天和 21 天)中检测到上调的 CD8 T 细胞,表明胸腺可能为 PBL 提供 CD8 T 细胞的输出,这与病毒清除有关。此外,在 PBL 中观察到上调的趋化因子 CXCLi1 在 7 天,这可能与 CD8 T 细胞从胸腺迁移到 PBL 有关。更重要的是,CD8αβ 表型的 CD8 T 细胞反应可能会产生颗粒酶 K、NK 溶素或 IFN-γ 来清除病毒。这些发现为开发有效的 ALV-J 疫苗提供了新的见解和方向。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/118f/7019883/385b6a57d9e8/viruses-12-00114-g001.jpg

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