Optimization of oncolytic effect of Newcastle disease virus Clone30 by selecting sensitive tumor host and constructing more oncolytic viruses
Authors: Deshan Li
Rui Sun
Zhenqiu Gao
Guangchao Sui
Wenying Sun
Zhenzhong Wang
Yukai Cao
Guiping Ren
Jiechao Yin
Qingzhong Yu
Tianyan Liu
Shan Jiang
Wei Xiao
Yu Zhang
Xu Sun
Journal: Gene Therapy (2021)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Newcastle disease virus; oncolytic effect; cancer cells; susceptibility; virus infection
Affiliations: College of Life Science, Northeast Agricultural University, Harbin, 150030, China., Jiangsu Kanion Parmaceutical CO. LTD, State Key Laboratory of New-tech for Chinese Medicine Pharmaceutical Process, Lianyungang, 222001, Jiangsu, China., School of Pharmacy, Yancheng Teachers University, Yancheng, 224007, China., Southeast Poultry Research Laboratory, Agricultural Research Service, United States Department of Agriculture, 934 College Station Road, Athens, GA, 30605, USA., College of Life Science, Northeast Forestry University, Harbin, 150040, China., Jiangsu Kanion Parmaceutical CO. LTD, State Key Laboratory of New-tech for Chinese Medicine Pharmaceutical Process, Lianyungang, 222001, Jiangsu, China. ., College of Life Science, Northeast Agricultural University, Harbin, 150030, China. .

Abstract:  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. 

Retracted: No

PubPeer comments:
 Figure 2A: From my reading of this figure, these panels should show cells in different treatment conditions. The same structure seems to appear in both, I ve added the magenta rectangles to show where I mean. Would the authors please comment? ![file] , 
 Figure 2A: When you increase the brightness and contrast on the HepG2 and SH-SY5Y control cells, it appears that most of the hidden features are in the same similar position between these panels. I think this is an unexpected similarity, the location of bright spots shouldn t follow any pattern. Would the authors please comment? ![file] ,