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腺病毒载体表达犬干扰素 λ3 能有效诱导抗犬流感病毒的抗病毒活性。

Canine interferon lambda 3 expressed using an adenoviral vector effectively induces antiviral activity against canine influenza virus.

机构信息

Department of Infectious Diseases, College of Veterinary Medicine, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul, 05029, Republic of Korea.

Department of Infectious Diseases, College of Veterinary Medicine, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul, 05029, Republic of Korea.

出版信息

Virus Res. 2021 Apr 15;296:198342. doi: 10.1016/j.virusres.2021.198342. Epub 2021 Feb 16.

Abstract

Interferon-lambda (IFN-λ) is a type-III IFN and is considered a candidate of antiviral therapeutics. Although the antiviral effects of IFN-λ have been investigated in several studies, it has not been clinically approved as an antiviral agent. In this study, an adenoviral vector expression system employing a tetracycline-operator system was developed to control the expression of canine IFN-λ3. The antiviral effects of canine IFN-λ3 were determined in Madin-Darby canine kidney cells and canine tracheal epithelial cells. After transducing each cell line with recombinant adenovirus containing canine interferon lambda3 gene (Ad-caIFNλ3), the mRNA-expression of interferon-stimulated genes Mx1, ISG15, and OAS1 increased significantly (P < 0.05). The replication of canine influenza virus (CIV) was significantly suppressed in Ad-caIFNλ3-infected cells. These results indicate that the newly constructed adenoviral vector system could express canine IFN-λ3, which could subsequently inhibit CIV replication in two canine cell lines. These data imply that the recombinant Ad-caIFNλ3 can potentially be used to treat canine influenza and other viral diseases.

摘要

干扰素 - λ(IFN-λ)是一种 III 型干扰素,被认为是抗病毒治疗的候选药物。尽管 IFN-λ 的抗病毒作用已在多项研究中进行了研究,但尚未被临床批准为抗病毒药物。在这项研究中,开发了一种使用四环素操纵子系统的腺病毒载体表达系统来控制犬 IFN-λ3 的表达。在 Madin-Darby 犬肾细胞和犬气管上皮细胞中测定了犬 IFN-λ3 的抗病毒作用。用含有犬干扰素 lambda3 基因的重组腺病毒(Ad-caIFNλ3)转导每种细胞系后,干扰素刺激基因 Mx1、ISG15 和 OAS1 的 mRNA 表达显著增加(P < 0.05)。犬流感病毒(CIV)的复制在 Ad-caIFNλ3 感染的细胞中被显著抑制。这些结果表明,新构建的腺病毒载体系统可以表达犬 IFN-λ3,随后可以抑制两种犬细胞系中的 CIV 复制。这些数据表明,重组 Ad-caIFNλ3 可用于治疗犬流感和其他病毒疾病。

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