title: Newcastle disease virus chimeras expressing the Hemagglutinin- Neuraminidase protein of mesogenic strain exhibits an enhanced anti-hepatoma efficacy.
abstract: Newcastle disease virus (NDV) is an intrinsically tumor-specific virus, many researchers have reported that lentogenic NDV is a safe and effective agent for human cancer therapy. It had been demonstrated that the amino acid sequence of the fusion protein cleavage site is a major factor in the pathogenicity and anti-tumor efficacy of rNDV. However, the role of Hemagglutinin-Neuraminidase (HN) gene that contributes to virulence and anti-tumor efficacy remains undefined. To assess the role of HN gene in virus pathogenicity and anti-tumor efficacy, a reverse genetic system was developed using the lentogenic NDV Clone30 strain to provide backbone for gene exchange. Chimeric virus (rClone30-Anh(HN)) created by exchange of the HN gene of lentogenic strain Clone30 with HN gene of mesogenic strain produce no significant changes in virus pathogenicity as assessed by conducting the mean death time (MDT) and intracerebral pathogenicity index (ICPI) assays. In vitro, infection with chimeras could induce the formation of syncytium relative significantly in HepG2 cells. Furthermore, chimeras was shown to induce the cell apoptosis via MTT and Annexin V-PI assays, reduce mitochondrial membrane potential and increase the mRNA transcription level of caspase 3. In vivo, ICR mice carrying tumor of hepatoma H22 cells were treated via intratumoral injection of chimeric virus. The treatment of chimera shows an obvious suppression in tumor volume. These results suggest that it could be an ideal approach to enhance the antitumor ability of Newcastle disease virus and highlighted the potential therapeutic application of rClone30-Anh(HN) as a viral vector to deliver foreign genes for treatment of cancers.
authors.affiliation: College of Life Science, Northeast Agriculture University, Mucai Street 59, Xiangfang district, Harbin, PR China.
authors.forename: Jinjiao
authors.initials: J
authors.lastname: He
authors.affiliation: College of Biological Science and Technology, Heilongjiang Bayi Agricultural University, Daqing, 163319, PR China.
authors.forename: Ziye
authors.initials: Z
authors.lastname: Pan
authors.affiliation: College of Life Science, Northeast Agriculture University, Mucai Street 59, Xiangfang district, Harbin, PR China.
authors.forename: Guiyou
authors.initials: G
authors.lastname: Tian
authors.affiliation: College of Life Science, Northeast Agriculture University, Mucai Street 59, Xiangfang district, Harbin, PR China.
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.affiliation: College of Life Science, Northeast Agriculture University, Mucai Street 59, Xiangfang district, Harbin, PR China.
authors.forename: Yunye
authors.initials: Y
authors.lastname: Liu
authors.affiliation: College of Life Science, Northeast Agriculture University, Mucai Street 59, Xiangfang district, Harbin, PR China.
authors.forename: Xiaochen
authors.initials: X
authors.lastname: Guo
authors.affiliation: College of Life Science, Northeast Agriculture University, Mucai Street 59, Xiangfang district, Harbin, PR China.
authors.forename: Ying
authors.initials: Y
authors.lastname: An
authors.affiliation: College of Life Science, Northeast Agriculture University, Mucai Street 59, Xiangfang district, Harbin, PR China.
authors.forename: Liying
authors.initials: L
authors.lastname: Song
authors.affiliation: College of Life Science, Northeast Agriculture University, Mucai Street 59, Xiangfang district, Harbin, PR China.
authors.forename: Hongsong
authors.initials: H
authors.lastname: Wu
authors.affiliation: College of Biological Science and Technology, Heilongjiang Bayi Agricultural University, Daqing, 163319, PR China.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Cao
authors.affiliation: College of Life Science, Northeast Agriculture University, Mucai Street 59, Xiangfang district, Harbin, PR China.
authors.forename: Dan
authors.initials: D
authors.lastname: Yu
authors.affiliation: College of Life Science, Northeast Agriculture University, Mucai Street 59, Xiangfang district, Harbin, PR China.
authors.forename: Ruixiang
authors.initials: R
authors.lastname: Che
authors.affiliation: College of Life Science, Northeast Agriculture University, Mucai Street 59, Xiangfang district, Harbin, PR China.
authors.forename: Pengfei
authors.initials: P
authors.lastname: Xu
authors.affiliation: College of Life Science, Northeast Agriculture University, Mucai Street 59, Xiangfang district, Harbin, PR China; College of science, university of Baghdad, Baghdad, Iraq.
authors.forename: Lubna M
authors.initials: LM
authors.lastname: Rasoul
authors.affiliation: College of Life Science, Northeast Agriculture University, Mucai Street 59, Xiangfang district, Harbin, PR China. Electronic address: deshanli@163.com.
authors.forename: Deshan
authors.initials: D
authors.lastname: Li
authors.affiliation: College of Life Science, Northeast Agriculture University, Mucai Street 59, Xiangfang district, Harbin, PR China. Electronic address: 738530221@qq.com.
authors.forename: Jiechao
authors.initials: J
authors.lastname: Yin
mesh_terms: D000818:Animals; D017209:Apoptosis; D006528:Carcinoma, Hepatocellular / Q000628:therapy*; D004195:Disease Models, Animal; D015707:HN Protein / Q000235:genetics* / Q000378:metabolism*; D056945:Hep G2 Cells; D006801:Humans; D008813:Mice, Inbred ICR; D009522:Newcastle disease virus / Q000235:genetics* / Q000254:growth & development*; D050130:Oncolytic Virotherapy / Q000379:methods*; D059386:Reverse Genetics; D016896:Treatment Outcome
chemical_list: D015707:HN Protein
keywords: Anti-hepatoma; Apoptosis; Hemagglutinin-neuraminidase; Recombinant newcastle disease virus