Optimization of oncolytic effect of Newcastle disease virus Clone30 by selecting sensitive tumor host and constructing more oncolytic viruses.
Optimization of oncolytic effect of Newcastle disease virus Clone30 by selecting sensitive tumor host and constructing more oncolytic viruses.
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选择敏感肿瘤宿主并构建更多溶瘤病毒优化新城疫病毒Clone30溶瘤效果
DOI：
10.1038/s41434-020-0145-9
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发表时间：
2021-12
期刊：
影响因子：
5.1
通讯作者：
Li D
中科院分区：
文献类型：
--
作者：
Liu T;Zhang Y;Cao Y;Jiang S;Sun R;Yin J;Gao Z;Ren G;Wang Z;Yu Q;Sui G;Sun X;Sun W;Xiao W;Li D
纽卡斯尔病毒（NDV）的直接溶瘤作用取决于以下两个方面：癌细胞对病毒感染的易感性和病毒本身裂解癌细胞的能力。首先，我们研究了癌细胞对NDV感染的敏感性，HepG 2、MDA-MB-231和SH-SY 5 Y细胞是敏感的，A549、MCF 7和LoVo细胞是不太敏感的。为了研究负责癌细胞易感性的分子机制，进行了转录组测序。我们发现，与MCF 7细胞相比，MDA-MB-231细胞中α-唾液酸酰基转移酶的水平上调，而干扰素的水平下调。第二，为了优化野生型rClone 30的溶瘤能力，通过将非裂解性rClone 30株的HN基因、F基因或两者与裂解性菌株Anhinga交换，构建了一系列嵌合病毒rClone 30-Anh（HN）、rClone 30-Anh（F）和rClone 30-Anh（HN-F）。rClone 30-Anh（F）和rClone 30-Anh（HN-F）增强了rClone 30的溶瘤作用，并且这种增强在敏感细胞中更明显。通过转录组分析rClone 30-Anh（F）的溶瘤机制，与rClone 30相比，rClone 30-Anh（F）上调ATG 5、Beclin 1和MAP 1 LC 3B的表达，从而激活自噬，促进合胞体的产生。总之，我们的研究提供了增强rClone 30的溶瘤作用的策略。
The direct oncolytic effect of Newcastle disease virus (NDV) depends on the following two aspects: the susceptibility of cancer cells to virus infection and the ability of virus itself to lyse cancer cells. First, we investigate the susceptibility of cancer cells to NDV infection, HepG2, MDA-MB-231, and SH-SY5Y cells were susceptible, A549, MCF7, and LoVo cells were less susceptible. To investigate the molecular mechanism responsible for cancer cell susceptibility, transcriptome sequencing was carried out. We found that the levels of alpha-sialic acid acyltransferase were upregulated in MDA-MB-231 cells compared with MCF7 cells, and the interferon was downregulated. Second, to optimize the oncolytic capacity of the wild-type rClone30, a series of chimeric viruses rClone30-Anh(HN), rClone30-Anh(F), and rClone30-Anh(HN-F) were constructed by exchanging the HN gene, F gene or both of non-lytic rClone30 strain with lytic strain Anhinga. rClone30-Anh(F) and rClone30-Anh(HN-F) enhanced the oncolytic effect of the rClone30, and this enhancement is more obvious in the susceptible cells. The oncolytic mechanism of rClone30-Anh(F) was analyzed by transcriptome analyses, in comparison with rClone30, rClone30-Anh(F) upregulated the expression of ATG5, Beclin 1, and MAP1LC3B, thus activating autophagy and promoting the production of syncytia. In conclusion, our study provides a strategy to enhance the oncolytic effect of rClone30.
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影响因子：
4.8
作者：
de Araujo, Mariana E. G.;Stasyk, Taras;Huber, Lukas A.
通讯作者：
Huber, Lukas A.
影响因子：
21.3
作者：
通讯作者：
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新城疫病毒诱导的自噬介导体内外抗凋亡信号反应
影响因子：
--
作者：
Kang Y;Yuan R;Xiang B;Zhao X;Gao P;Dai X;Liao M;Ren T
通讯作者：
Ren T
DOI：
10.1038/nrmicro1927
发表时间：
2008-07
期刊：
Nature reviews. Microbiology
影响因子：
--
作者：
通讯作者：
--
影响因子：
3.7
作者：
Bose, Sayantan;Jardetzky, Theodore S.;Lamb, Robert A.
通讯作者：
Lamb, Robert A.