Chichen type III interferon produced by silkworm bioreactor induces ISG expression and restricts ALV-J infection in vitro

Chichen type III interferon produced by silkworm bioreactor induces ISG expression and restricts ALV-J infection in vitro
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家蚕生物反应器产生的Chichen III型干扰素诱导ISG表达并限制ALV-J体外感染

DOI:
10.1007/s00253-019-10090-z
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发表时间:
2019-10-01
影响因子:
5
通讯作者:
Sun, Jingchen
Sun, Jingchen
中科院分区:
工程技术2区
文献类型:
--
作者:
Feng, Min;Zhang, Nan;Sun, Jingchen

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III型干扰素(IFN-lambda)最近被证明对脊椎动物的病毒具有显著的抗病毒作用。禽白血病病毒J亚群(ALV-J)是一种由于缺乏疫苗和药物而难以预防和控制的逆转录病毒,可引起感染鸡的肿瘤疾病和免疫抑制。在此,我们利用家蚕生物反应器获得了鸡IFN-lambda (chIFN-lambda),并证明了chIFN-lambda对鸡胚成纤维细胞系(DF1)和上皮细胞系(LMH)的ALV-J感染均具有抗病毒活性。我们发现chIFN-lambda在DF1和LMH细胞中触发了更高水平的特定III型干扰素刺激基因(III型ISGs),包括黏液病毒抗性蛋白(Mx)、viperin (RSAD2)和干扰素诱导跨膜蛋白3 (IFITM3)。此外,过表达Mx、viperin和IFITM3可以抑制ALV-J在DF1和LMH细胞中的感染。因此,这些结果表明chIFN-lambda的抗alv - j功能是通过诱导III型ISGs的表达特异性实现的。我们的数据确定了chIFN-lambda是ALV-J感染的关键抗病毒药物,并为商业化生产chIFN-lambda提供了一个潜在的和有吸引力的平台。
Type III interferon (IFN-lambda) has recently been shown to exert a significant antiviral impact against viruses in vertebrates. Avian leukosis virus subgroup J (ALV-J), which causes tumor disease and immunosuppression in infected chicken, is a retrovirus that is difficult to prevent and control because of a lack of vaccines and drugs. Here, we obtained chicken IFN-lambda (chIFN-lambda) using a silkworm bioreactor and demonstrated that chIFN-lambda has antiviral activity against ALV-J infection of both chicken embryo fibroblast cell line (DF1) and epithelial cell line (LMH). We found that chIFN-lambda triggered higher levels of particular type III interferon-stimulated genes (type III ISGs) including myxovirus resistance protein (Mx), viperin (RSAD2), and interferon-inducible transmembrane protein 3 (IFITM3) in DF1 and LMH cells. Furthermore, over-expression of Mx, viperin, and IFITM3 could inhibit ALV-J infection in DF1 and LMH cells. Therefore, these results suggested that the anti-ALV-J function of chIFN-lambda was specifically implemented by induction of expression of type III ISGs. Our data identified chIFN-lambda as a critical antiviral agent of ALV-J infection and provides a potentially and attractive platform for the production of commercial chIFN-lambda.