Systematic Identification of Host Immune Key Factors Influencing Viral Infection in PBL of ALV-J Infected SPF Chicken
Systematic Identification of Host Immune Key Factors Influencing Viral Infection in PBL of ALV-J Infected SPF Chicken
复制标题
ALV-J感染SPF鸡PBL中影响病毒感染的宿主免疫关键因素的系统鉴定
DOI：
10.3390/v12010114
复制
发表时间：
2020-01-01
期刊：
影响因子：
4.7
通讯作者：
Liao, Ming
中科院分区：
文献类型：
--
作者：
Dai, Manman;Li, Shibing;Liao, Ming
J亚群禽白血病病毒（ALV-J）的研究已有世纪之久，但系统鉴定宿主抗ALV-J感染的免疫关键因子尚未见报道。本研究建立了ALV-J CHN 06株感染4周龄SPF鸡的感染模型，并检测了感染后宿主的免疫应答。结果发现，ALV-J感染的外周血淋巴细胞（PBL）中两个抗病毒干扰素刺激基因（ISGs）（Mx 1和IFIT 5）的表达增加。J株ALV-J感染后7 d即出现明显的CD 8 + T细胞免疫应答，21 d开始的体液免疫应答在时间上差异较大。同时，ALV-J病毒血症在14 DPI抗体产生前显著降低，并在极低抗体水平下在21 DPI消除。在胸腺（14 DPI）和PBL（7 DPI和21 DPI）中检测到上调的CD 8 + T细胞，表明胸腺可能向PBL提供CD 8 + T细胞的输出，这与病毒清除有关。此外，在7 DPI时观察到PBL中的趋化因子CXCLi 1上调，这可能与CD 8 + T细胞从胸腺向PBL的迁移有关。更重要的是，CD 8 αβ表型的CD 8高+ T细胞应答可产生颗粒酶K、NK溶素或IFN-γ以清除病毒。这些发现为开发有效的ALV-J疫苗提供了新的见解和方向。
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 high+ 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.