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一种编码 IFN-γ 的人腺病毒可以转导袋獾面部肿瘤细胞,并上调 MHC-I。

A human adenovirus encoding IFN-γ can transduce Tasmanian devil facial tumour cells and upregulate MHC-I.

机构信息

Menzies Institute for Medical Research, University of Tasmania, 17 Liverpool Street, Hobart, TAS, 7000, Australia.

Department of Science and Laboratory Technology, Dar es Salaam Institute of Technology, Bibititi and Morogoro Rd Junction, P. O. Box 2958, Dar-es-salaam, Tanzania.

出版信息

J Gen Virol. 2022 Nov;103(11). doi: 10.1099/jgv.0.001812.

DOI:10.1099/jgv.0.001812
PMID:36382885
Abstract

The devil facial tumour disease (DFTD) has led to a massive decline in the wild Tasmanian devil () population. The disease is caused by two independent devil facial tumours (DFT1 and DFT2). These transmissible cancers have a mortality rate of nearly 100 %. An adenoviral vector-based vaccine has been proposed as a conservation strategy for the Tasmanian devil. This study aimed to determine if a human adenovirus serotype 5 could express functional transgenes in devil cells. As DFT1 cells do not constitutively express major histocompatibility complex class I (MHC-I), we developed a replication-deficient adenoviral vector that encodes devil interferon gamma (IFN-γ) fused to a fluorescent protein reporter. Our results show that adenoviral-expressed IFN-γ was able to stimulate upregulation of beta-2 microglobulin, a component of MHC-I, on DFT1, DFT2 and devil fibroblast cell lines. This work suggests that human adenoviruses can serve as a vaccine platform for devils and potentially other marsupials.

摘要

恶魔面部肿瘤病(DFTD)导致野生袋獾数量大幅减少。这种疾病由两种独立的恶魔面部肿瘤(DFT1 和 DFT2)引起。这些传染性癌症的死亡率接近 100%。腺病毒载体疫苗被提议作为袋獾的保护策略。本研究旨在确定人腺病毒 5 型能否在袋獾细胞中表达功能性转基因。由于 DFT1 细胞不持续表达主要组织相容性复合体 I(MHC-I),我们开发了一种复制缺陷型腺病毒载体,该载体编码与荧光蛋白报告基因融合的袋獾干扰素 γ(IFN-γ)。我们的结果表明,腺病毒表达的 IFN-γ能够刺激 DFT1、DFT2 和袋獾成纤维细胞系中 MHC-I 的组成部分β-2 微球蛋白的上调。这项工作表明,人类腺病毒可以作为袋獾和其他有袋动物的疫苗平台。

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A human adenovirus encoding IFN-γ can transduce Tasmanian devil facial tumour cells and upregulate MHC-I.一种编码 IFN-γ 的人腺病毒可以转导袋獾面部肿瘤细胞,并上调 MHC-I。
J Gen Virol. 2022 Nov;103(11). doi: 10.1099/jgv.0.001812.
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