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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。

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

机构信息

Guangdong Provincial Key Laboratory of Agro-Animal Genomics and Molecular Breeding, College of Animal Science, South China Agricultural University, No. 483 Wushan Road, Tianhe District, Guangzhou, 510642, People's Republic of China.

Insect Molecular Genetics and Biotechnology, Institute of Biosciences and Applications, National Centre for Scientific Research Demokritos, Aghia Paraskevi, 15341, Athens, Greece.

出版信息

Appl Microbiol Biotechnol. 2019 Oct;103(20):8473-8483. doi: 10.1007/s00253-019-10090-z. Epub 2019 Aug 29.

Abstract

Type III interferon (IFN-λ) 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-λ (chIFN-λ) using a silkworm bioreactor and demonstrated that chIFN-λ has antiviral activity against ALV-J infection of both chicken embryo fibroblast cell line (DF1) and epithelial cell line (LMH). We found that chIFN-λ 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-λ was specifically implemented by induction of expression of type III ISGs. Our data identified chIFN-λ as a critical antiviral agent of ALV-J infection and provides a potentially and attractive platform for the production of commercial chIFN-λ.

摘要

III 型干扰素(IFN-λ)最近被证明对脊椎动物病毒具有显著的抗病毒作用。禽白血病病毒亚群 J(ALV-J)是一种逆转录病毒,可引起感染鸡的肿瘤疾病和免疫抑制,由于缺乏疫苗和药物,因此难以预防和控制。在这里,我们使用蚕生物反应器获得了鸡 IFN-λ(chIFN-λ),并证明 chIFN-λ 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-λ 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),包括流感病毒抗性蛋白(Mx)、 viperin(RSAD2)和干扰素诱导跨膜蛋白 3(IFITM3)。此外,Mx、viperin 和 IFITM3 的过表达可以抑制 DF1 和 LMH 细胞中的 ALV-J 感染。因此,这些结果表明 chIFN-λ 的抗 ALV-J 功能是通过诱导 III 型 ISGs 的表达来特异性实现的。我们的数据将 chIFN-λ 鉴定为 ALV-J 感染的关键抗病毒剂,并为生产商业 chIFN-λ 提供了一个有潜力和有吸引力的平台。

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