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SP600125 通过阻断 JNK MAPK 通路抑制禽腺病毒 4 型在来亨公鸡肝癌细胞中的复制。

Inhibition of fowl adenovirus serotype 4 replication in Leghorn male hepatoma cells by SP600125 via blocking JNK MAPK pathway.

机构信息

State Key Laboratory of Agrobiotechnology and College of Veterinary Medicine, China Agricultural University, Beijing, 100193, China; Key Laboratory of Animal Epidemiology in the Ministry of Agriculture, China Agricultural University, Beijing, 100193, China.

State Key Laboratory of Agrobiotechnology and College of Veterinary Medicine, China Agricultural University, Beijing, 100193, China.

出版信息

Vet Microbiol. 2019 Jan;228:45-52. doi: 10.1016/j.vetmic.2018.11.014. Epub 2018 Nov 18.

Abstract

Fowl Adenoviruses (FAdVs) are widely-distributed pathogens across the globe. Fowl adenovirus serotype 4 (FAdV-4), the causative agent for chicken hydropericardium syndrome (HPS) with a high mortality in the infected flocks, has caused severe economic losses to the poultry industry of China in the past few years. Although vaccination against FAdV-4 has been implemented, the prevention and control of FAdV-4 infection is still not very successful. Here, we report that FAdV-4 markedly inhibits Leghorn male hepatoma (LMH) cell growth and this inhibition could be abolished by a small molecule SP600125, a JNK MAPK specific inhibitor. Furthermore, SP600125 considerably suppressed FAdV-4-induced phosphorylation of p38 and JNK MAPK. Importantly, SP600125 promoted type I interferon production associated with inhibition of FAdV-4 replication. Thus, FAdV-4 might employ the JNK MAPK pathway for the benefit of its replication, and SP600125 may have the potential of being used as an anti-virus drug for the control FAdV-4 infection.

摘要

禽腺病毒(FAdV)在全球范围内广泛分布。禽腺病毒血清型 4(FAdV-4)是引起鸡包涵体肝炎综合征(HPS)的病原体,在感染鸡群中死亡率很高,近年来给中国家禽业造成了严重的经济损失。尽管已经实施了针对 FAdV-4 的疫苗接种,但 FAdV-4 感染的预防和控制仍不是非常成功。在这里,我们报告 FAdV-4 明显抑制莱杭雄性肝癌(LMH)细胞的生长,而这种抑制可以被一种小分子 SP600125 消除,SP600125 是一种 JNK MAPK 特异性抑制剂。此外,SP600125 显著抑制 FAdV-4 诱导的 p38 和 JNK MAPK 的磷酸化。重要的是,SP600125 促进了与抑制 FAdV-4 复制相关的 I 型干扰素的产生。因此,FAdV-4 可能利用 JNK MAPK 通路来促进其复制,而 SP600125 可能具有作为抗病毒药物来控制 FAdV-4 感染的潜力。

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