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The Stronger Downregulation of in vitro and in vivo Innate Antiviral Responses by a Very Virulent Strain of Infectious Bursal Disease Virus (IBDV), Compared to a Classical Strain, Is Mediated, in Part, by the VP4 Protein.
Frontiers in Cellular and Infection Microbiology ( IF 4.6 ) Pub Date : 2020-05-25 , DOI: 10.3389/fcimb.2020.00315
Katherine L Dulwich 1, 2 , Amin Asfor 1 , Alice Gray 1 , Efstathios S Giotis 2, 3 , Michael A Skinner 2 , Andrew J Broadbent 1
Affiliation  

IBDV is economically important to the poultry industry. Very virulent (vv) strains cause higher mortality rates than other strains for reasons that remain poorly understood. In order to provide more information on IBDV disease outcome, groups of chickens (n = 18) were inoculated with the vv strain, UK661, or the classical strain, F52/70. Birds infected with UK661 had a lower survival rate (50%) compared to F52/70 (80%). There was no difference in peak viral replication in the bursa of Fabricius (BF), but the expression of chicken IFNα, IFNβ, MX1, and IL-8 was significantly lower in the BF of birds infected with UK661 compared to F52/70 (p < 0.05) as quantified by RTqPCR, and this trend was also observed in DT40 cells infected with UK661 or F52/70 (p < 0.05). The induction of expression of type I IFN in DF-1 cells stimulated with polyI:C (measured by an IFN-β luciferase reporter assay) was significantly reduced in cells expressing ectopic VP4 from UK661 (p < 0.05), but was higher in cells expressing ectopic VP4 from F52/70. Cells infected with a chimeric recombinant IBDV carrying the UK661-VP4 gene in the background of PBG98, an attenuated vaccine strain that induces high levels of innate responses (PBG98-VP4UK661) also showed a reduced level of IFNα and IL-8 compared to cells infected with a chimeric virus carrying the F52/70-VP4 gene (PBG98-VP4F52/70) (p < 0.01), and birds infected with PBG98-VP4UK661 also had a reduced expression of IFNα in the BF compared to birds infected with PBG98-VP4F52/70 (p < 0.05). Taken together, these data demonstrate that UK661 induced the expression of lower levels of anti-viral type I IFN and proinflammatory genes than the classical strain in vitro and in vivo and this was, in part, due to strain-dependent differences in the VP4 protein.



中文翻译:


与经典毒株相比,传染性法氏囊病病毒 (IBDV) 强毒株对体外和体内先天抗病毒反应的下调作用更强,部分是由 VP4 蛋白介导的。



IBDV 对家禽业具有重要的经济意义。剧毒(vv)菌株比其他菌株导致更高的死亡率,其原因仍知之甚少。为了提供有关 IBDV 疾病结果的更多信息,鸡群 (n = 18) 接种了 vv 菌株 UK661 或经典菌株 F52/70。与 F52/70 (80%) 相比,感染 UK661 的禽类存活率 (50%) 较低。法氏囊(BF)中的病毒复制峰值没有差异,但与 F52/70 相比,感染 UK661 的禽类 BF 中鸡 IFNα、IFNβ、MX1 和 IL-8 的表达显着降低(p < 0.05)通过 RTqPCR 定量,并且在感染 UK661 或 F52/70 的 DT40 细胞中也观察到这种趋势(p < 0.05)。在表达来自 UK661 的异位 VP4 的细胞中,用 PolyI:C 刺激的 DF-1 细胞(通过 IFN-β 荧光素酶报告测定法测量)中 I 型 IFN 表达的诱导显着降低 (p < 0.05),但在表达 F52/70 异位 VP4 的细胞。在PBG98(一种诱导高水平先天反应的减毒疫苗株(PBG98-VP4 UK661 ))背景下,用携带UK661-VP4基因的嵌合重组IBDV感染的细胞也显示出与细胞相比,IFNα和IL-8水平降低感染携带 F52/70-VP4 基因 (PBG98-VP4 F52/70 ) 的嵌合病毒 (p < 0.01) 的禽类,与感染禽类相比,感染 PBG98-VP4 UK661的禽类 BF 中 IFNα 的表达也降低与 PBG98-VP4 F52/70 (p < 0.05)。 总而言之,这些数据表明,在体外和体内,UK661 诱导的抗病毒 I 型 IFN 和促炎基因表达水平低于经典菌株,部分原因是 VP4 蛋白的菌株依赖性差异。

更新日期:2020-05-25
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