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newcastle disease virus suppresses antigen presentation via inhibiting IL-12 expression in dendritic cells

Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2024年第3期25卷 254-270页

作者： Fulong NAN Wenlong NAN Xin YAN Hui WANG Shasha JIANG Shuyun ZHANG Zhongjie YU Xianjuan ZHANG Fengjun LIU Jun LI Xiaoqiong ZHOU Delei NIU Yiquan LI Wei WANG Ning SHI Ningyi JIN Changzhan XIE Xiaoni CUI He ZHANG Bin WANG Huijun LU Department of Special Medicine Department of Pathogenic BiologySchool of Basic MedicineQingdao UniversityQingdao 266071China China Animal Health and Epidemiology Center Qingdao 266032China Academician Workstation of Jilin Province Changchun University of Chinese MedicineChangchun 130117China Institute of Virology Wenzhou UniversityWenzhou 325035China College of Veterinary Medicine Jilin UniversityChangchun 130012China Changchun Veterinary Research Institute Chinese Academy of Agricultural SciencesChangchun 130122China Sino-Cell Biomed Co. Ltd.Qingdao 266000China

As a potential vectored vaccine,newcastle disease virus(NDV)has been subject to various studies for vaccine development,while relatively little research has outlined the immunomodulatory effect of the virus in antigen *** elucidate the key inhibitory factor in regulating the interaction of infected dendritic cells(DCs)and T cells,DCs were pretreated with the NDV vaccine strain LaSota as an inhibitor and stimulated with lipopolysaccharide(LPS)for further detection by enzyme-linked immunosorbent assay(ELISA),flow cytometry,immunoblotting,and quantitative real-time polymerase chain reaction(qRT-PCR).The results revealed that NDV infection resulted in the inhibition of interleukin(IL)-12p40 in DCs through a p38 mitogen-activated protein kinase(MAPK)-dependent manner,thus inhibiting the synthesis of IL-12p70,leading to the reduction in T cell proliferation and the secretion of interferon-(IFN-),tumor necrosis factor-α(TNF-α),and IL-6 induced by ***,downregulated cytokines accelerated the infection and viral transmission from DCs to T ***,several other strains of NDV also exhibited inhibitory *** current study reveals that NDV can modulate the intensity of the innate-adaptive immune cell crosstalk critically toward viral invasion improvement,highlighting a novel mechanism of virus-induced immunosuppression and providing new perspectives on the improvement of NDV-vectored vaccine.

关键词： newcastle disease virus Dendritic cells Interleukin-12(IL-12) T cells Immunosuppression

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Partial Fusion (F) Gene Analysis of newcastle disease virus Detected in Pakistan during 2021-2022

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Journal of Biosciences and Medicines 2024年第5期12卷 256-275页

作者： Muhammad Danish Mehmood Huma Anwar Ul-Haq Rauf Khalid Yasir Amin Muhammad Usman Ghani Muhammad Ismail Rabia Habib Fareeha Arshed Abdul Rasheed Shaukat Institute of Molecular Biology & Biotechnology University of Lahore Lahore Pakistan Research & Development Division Ottoman Pharma Lahore Pakistan Quality Assurance Department Ottoman Pharma Lahore Pakistan Veterinary Research and disease Investigation Center Abbottabad Pakistan Quality Control Department Ottoman Pharma Immuno Lahore Pakistan Production Department Ottoman Pharma Lahore Pakistan Poultry Production Department Sabir&#8217s Poultry Pvt. Ltd. Sabroso Pakistan

newcastle disease (ND) virus is a leading threat to commercial and domestic poultry in Pakistan. The virus infects and constitutes irreversible impairment to the nervous system, damages the respiratory system, and marks severe gastrointestinal lesions leading to heavy mortality in short-living birds and substantial losses in layers and breeders. The continuous emergence and evolution of the virus made it inclined to evade the humoral response and indirectly the circumvention of artificial active immunization. newcastle disease is caused by the orthoavula genus of the paramyxoviridae family and has shown high genetic diversity even in their genotypes while information regarding enzootic trends of the virus is scanty in Pakistan. A total of 40 tracheal samples of NDV were collected from different commercial broiler farms and 11 isolates of NDV were identified. In the current study, we determined the genetic diversity of the newcastle disease virus based on the partial sequencing of the fusion protein gene available in the NCBI database. Genetic analysis showed that seven isolates belonged to class I genotype VII and four belonged to class II genotype II. Interestingly, two isolates had epidemiological connections with vaccine-like class II genotype II. Our findings, concerning the recent outbreaks of class I genotype VII and class II genotype II of NDV in vaccinated commercial flocks, suggest possible potential partial mutations in the fusion protein gene. Genetic diversity and formation of the new cleavage site in an important neutralizing protein of wild strain are linked with the potency of artificial active immunization and a major cause of vaccine failure.

关键词： newcastle disease virus Haemagglutination Inhibition Polymerase Chain Reaction Phylogenetic Tree Mutation Analysis

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Oncolytic Activity of Wild-type newcastle disease virus HK84 Against Hepatocellular Carcinoma Associated with Activation of Type I Interferon Signaling

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Journal of Clinical and Translational Hepatology 2022年第2期10卷 284-296页

作者： Liming Chen Yongdong Niu Jiating Sun Hong Lin Guoxi Liang Min Xiao Dongmei Shi Jia Wang Huachen Zhu Yi Guan Department of Oncology First Affiliated Hospital of Shantou University Medical CollegeShantouGuangdongChina In-ternational Joint Laboratory for Virology and Emerging Infectious diseases(Ministry of Education) Guangdong-Hong Kong Joint Laboratory for Emerging Infectious DiseasesJoint Institute of Virology of STU/HKUShantouGuangdongChina Department of Pharmacology Shantou University Medical CollegeShantouGuangdongChina

Background and Aims:Hepatocellular carcinoma(HCC)is listed as one of the most common causes of cancer-related *** therapy has become a promising treatment because of novel immunotherapies and gene editing technology,but biosafety concerns remain the biggest limitation for clinical *** studied the the antitumor activity and biosafety of the wild-type newcastle disease virus HK84 strain(NDV/HK84)and 10 other NDV ***-ods:Cell proliferation and apoptosis were determined by cell counting Kit-8 and fluorescein isothiocyanate Annexin V apoptosis *** formation,wound healing,and a xenograft mouse model were used to evaluate in vivo and in vitro oncolytic *** safety of NDV/HK84 was tested in nude mice by an in vivo luciferase imaging *** replication kinetics of NDV/HK84 in normal tis-sues and tumors were evaluated by infectious-dose assays in *** sequencing analysis was performed to explore NDV/HK84 activity and was validated by quantitative real-time ***:The cell counting Kit-8 assays of vi-ability found that the oncolytic activity of the NDV strains differed with the multiplicity of infection(MOI).At an MOI of 20,the oncolytic activity of all NDV strains except the DK/JX/21358/08 strain was>80%.The oncolytic activities of the NDV/HK84 and DK/JX/8224/04 strains were>80%at both MOI=20 and MOI=*** NDV/HK84 had>80%oncolytic activities at both MOI=20 and MOI=*** chose NDV/HK84 as the candidate virus to test the oncolytic effect of NDV in HCC in the in vitro and in vivo ***/HK84 killed human SK-HEP-1 HCC cells without affecting healthy ***:Intratumor infection with NDV/HK84 strains compared with vehicle controls or positive controls indicated that NDV/HK84 strain specifically inhib-ited HCC without affecting healthy ***-throughput RNA sequencing showed that the oncolytic activity of NDV/HK84 was dependent on the activation of type I interferon signaling.

关键词： newcastle disease virus Oncolytic effectiveness Type I interferon Hepatocellular carcinoma Biosafety

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newcastle disease virus-based MERS-CoV candidate vaccine elicits high-level and lasting neutralizing antibodies in Bactrian camels

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Journal of Integrative Agriculture 2017年第10期16卷 2264-2273页

作者： LIU Ren-qiang GE Jin-ying WANG Jin-ling SHAO Yu ZHANG Hui-lei WANG Jin-liang WEN Zhi-yuan BU Zhi-gao State Key Laboratory of Veterinary Biotechnology Harbin Veterinary Research Institute Chinese Academy of Agricultural Sciences Harbin 150069 P.R.China College of Veterinary Medicine Inner Mongolia Agricultural University Hohhot 010018 P.R. China

Middle East respiratory syndrome coronavirus （MERS-CoV）, a member of the Coronavifidae family, is the causative pathogen for MERS that is characterized by high fever, pneumonia, acute respiratory distress syndrome （ARDS）, as well as extrapul- monary manifestations. Currently, there are no approved treatment regimens or vaccines for MERS. Here~ we generated recombinant nonvirulent newcastle disease virus （NDV） LaSota strain expressing MERS-CoV S protein （designated as rLa- MERS-S）, and evaluated its immunogenicity in mice and Bactrian camels. The results revealed that rLa-MERS-S showed similar growth properties to those of LaSota in embryonated chicken eggs, while animal immunization studies showed that rLa-MERS-S induced MERS-CoV neutralizing antibodies in mice and camels. Our findings suggest that recombinant rLa- MERS-S may be a potential MERS-CoV veterinary vaccine candidate for camels and other animals affected by MERS.

关键词： newcastle disease virus MERS-CoV neutralizing antibodies camels

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A recombinant newcastle disease virus expressing MMP8 promotes oncolytic efficacy

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Chinese Chemical Letters 2021年第12期32卷 3962-3966页

作者： Tong Guo Xiuli Liu Zhikun Zhang Yiqun Luo Tong Li Lan Li Huixue Wang Yong Huang Jian He Qiaoying Chen Yongxiang Zhao Lu Gan Liping Zhong National Center for International Research of Biotargeting Theranostics Guangxi Key Laboratory of Biotargeting TheranosticsCollaborative Innovation Center for Targeting Tumor Diagnosis and TherapyGuangxi Talent Highland of Biotargeting TheranosticsGuangxi Medical UniversityNanning 530021China

Oncolytic virus is an emerging anti-cancer strategy. However, extracellular matrix(ECM), as a physical barrier, limits virus spread within the tumor. To overcome the obstacle, we constructed a recombinant newcastle disease virus(NDV) expressing matrix metalloproteinase(MMP8)(NDV-MMP8) using with reverse genetic technology. In vitro, NDV-MMP8 was identified and verified by WB and ELISA. Cell viability was detected by CCK-8 assay. In vivo, we established two liver cancer xenograft models. NDV-MMP8 was injected into the tumor to observe the tumor volume and survival of mice. The changes in extracellular matrix were observed by Masson’s trichrome staining. virus expression in tumor tissues was detected by immunofluorescence assay. The virus titer in tumor tissues was detected by TCID50. Histopathological changes were detected by hematoxylin and eosin(HE) and terminal deoxynucleotidyl transferase d UTP nick end labeling(TUNEL) staining. Intratumoral administration of NDV-MMP8 can effectively degrade ECM, promote the spread of the virus within the tumor, and reduce tumor growth rate. Therefore, the method of increasing intratumoral virus accumulation by degradation of the ECM to enhance the oncolytic effect has great potential for clinical application.

关键词： Oncolytic virus newcastle disease virus Matrix metalloproteinase 8 Extracellular matrix Cancer treatment

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Activity of T Cells Stimulated by Hemagglutinin-neuraminidase of newcastle disease virus in vivo

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Chemical Research in Chinese Universities 2011年第3期27卷 455-460页

作者： PIAO Bing-guo LI Xiao SUN Li-li KAN Shi-fu LIU Lei HUANG Hai-yan YANG Guo-hua WANG Yu-hang WANG Zhuo-yue SUN Jiu-hua PIAO Yun-feng JIN Ning-yi The First Hospital of Jilin University Changehun 130021 P. R. ChinA Genetic Engineering Laboratory of PLA 3. Key Laboratory of Jilin Province for Zoonosis Prevention and Control Military Veterinary Institute Academy of Military Medical Sciences of PLA Changehun 130062 P. R. China Key Laboratory of Jilin Province for Zoonosis Prevention and Control Military Veterinary Institute Academy of Military Medical Sciences of PLA Changchun 130062 P. R. China Department of Gastroenterology 209 Hospital of PLA Mudanjiang 157000 P. R. China Head and Neck Surgery Tumor Hospital of Jilin Province Changchun 130001 P R. China

To investigate the stimulated activity of T cells and the anti-tumor properties of hemagglutinin-neuraminidase（HN） of newcastle disease virus（NDV） strain Changchun（NDVcc）, the expression of HN gene in hepatoma cells（human HepG-2 and mouse H22 cells） infected with the recombinant adenovirus（Ad-HN） was identified by Western blot analysis and flow cytometry. Sialidase activity of NDVcc HN expressed by Ad-HN was assayed by the periodate-resorcinol method. The in vivo anti-tumor effects of NDVcc HN were evaluated in the H22 solid tumor model. Regional lymph nodes of the mouse model treated with Ad-HN were removed to harvest T lymphocytes and evaluating the specific cytotoxicity of cytotoxic T lymphocyte（CTL） and natural killer（NK） cells by an L-lactate dehydrogenase（LDH） assay, in the mean time, the secretion of cytokines was analyzed by enzyme linked immunosorbent assays（ELISA）. The results show that NDVcc HN was effectively expressed by Ad-HN in HepG-2 and H22 cells. The sialidase activity assay showed that Ad-HN significantly reduced sialic acid level of the hepatoma cells compared with the cells infected the empty adenovirus vector（Ad-mock）. When treated with Ad-HN, the growth of subcutaneous H22 primary tumors in C57BL/6 mice was suppressed, and the mean mice survival increased. In addition, the treatment of Ad-HN elicited strong NK and CTL responses, and high levels of Th1 cytokines, such as IL-2 and IFN-γ. In conclusion, NDVcc HN effectively elicits T cell-mediate anti-tumor cytotoxicity via sialidase activity and may be a novel strategy for cancer immunotherapy.

关键词： newcastle disease virus Hemagglutinin-neuraminidase Hepatoma T Cell Anti-tumor immunity

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Complete Nucleotide Sequence of a Newly Avirulent newcastle disease virus Hubei 92(HB92) Strain

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Wuhan University Journal of Natural Sciences 2004年第3期9卷 381-387页

作者： PanZi-shu ChenYu-dong ShaoHua-bin YangJun XiongZhong-liang WenGuo-yuan ZhangChu-yu CollegeofLifeSciences WuhanUniversityWuhan430072HubeiChina InstituteofAnimalHusbandryandVeterinaryScience HubeiAcademyofAgriculturalScienceWuhan430209HubeiChina

A new avirulent, heat-resistance HB92 strain of newcastle disease virus (NDV) was acquired from Australia V4 strain. Its complete nucleotides sequence was first determined. The entire genome of NDV HB92 consists of 15 186 nucleotides (GenBank accession no. AY225110). It was demonstrated by sequence analysis that nucleotides homology of HB92 strain with virulent strain ZJ1 were 83.9%, and the homology compared with avirulent vaccine strain La Sota and B1 were 94.0% and 93.5%, respectively. These results might be contributive to the study of the molecular mechanism of evolution of the NDV strain HB92 and to develop the engineered recombinant vaccine. Key words newcastle disease virus - genomic sequence - sequence analysis CLC number S 852. 65 Foundation item: Supported by Hubei Natural Science Foundation (2002AB144)Biography: Pan Zhi-shu(1961-), male, Ph. D, Associate professor, research direction: molecular biology and pathogenesis of eucaryotic viruses.

关键词： newcastle disease virus genomic sequence sequence analysis

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PLASMID VACCINE ENCODING HN GENE FROM newcastle disease virus HAS MARKED ANTITUMORAL EFFECT IN VITRO

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Chinese Journal of Cancer Research 2003年第3期15卷 161-166页

作者：薛立娟金宁一龚伟王宏伟李萍 Quartermaster University of PLA Changchun 130062

Objective: To explore the antitumor effects of hemaagglutinin-neuraminase gene (HN gene) from newcastle disease virus. Methods: Plasmid vaccine of pIRHN was constructed and transfected into HeLa cells. The expression of HN was analyzed by Western blot analysis, and the mode of cell death was detected by fluorescence microscope, gel electrophoresis and TUNEL assay and the expression of p53 and bcl-2 was also analyzed in transfected Hela cells. The effect of pIRHN on sialic acid contents in the Hela cell was examined. Results: pIRHN nucleic acid vaccines could be expressed in eukaryotic cell. pIRHN could induce apoptosis after HeLa cells were transfected. The effect of antitumor responses of pIRHN was correlated with the contents of sialic acid in tumor cells, and there was no prominent evidence for the relatedness of the antitumor effect with the expression of p53 and bcl-2. Conclusion: pIRHN may become a new antitumor biological agent.

关键词： newcastle disease virus Hemaagglutinin- neuraminase gene Western blot Antitumor effect Nucleic acid vaccines Apoptosis

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Modification of the full-length cDNA clone of newcastle disease virus isolated from an outbreak in the goose

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Frontiers in Biology 2006年第4期1卷 389-393页

作者： LIU Yuliang HU Shunli ZHANG Yanmei WU Yantao LIU Xiufan Röemer-Oberdoerfer Angela Veits Jutta Lange Martina Key Laboratory of Animal Infectious diseases Ministry of AgricultureYangzhou UniversityYangzhou 225009China Institute of Molecular Biology Friedrich-Loeffler-InstitutesFederal Research Centre for Virus Diseases of AnimalsD-17498 Insel RiemsGermany

A 6.5-kb specific fragment containing the T7 promoter and the transcription vector was excised from the full-length cDNA clone of the newcastle disease virus(NDV)strain ZJI of goose origin,and thereafter it was self-ligated to form a high quality plasmid for ***-directed mutagenesis was used for inserting three additional G nucleotides(nts)into the region between the T7 promoter and the leader sequence of the NDV ***-PCR was employed to amplify the F/HN gene fragments,and then they were ligated by the shared restriction enzyme ***,the corresponding fragment in the mutant full-length cDNA was substituted with the new *** sequencing results showed that the three additional G nts were successfully inserted and the mutant nts in the full-length cDNA were *** study lays a good foundation for research on the reverse genetics of NDV strain ZJI.

关键词： newcastle disease virus goose site-directed mutagenesis genomic cDNA clone modification

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newcastle disease virus NP and P proteins induce autophagy via the endoplasmic reticulum stress-related unfolded protein response

Newcastle disease virus NP and P proteins induce autophagy v...

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中国畜牧兽医学会兽医公共卫生学分会第五次学术研讨会

作者： Jing-Hua Cheng Ying-Jie Sun Fan-Qing Zhang Xiao-Rong Zhang Xv-Sheng Qiu Li-Ping Yu Yantao Wu Chan Ding Yangzhou University Shanghai Veterinary Research Institute CAAS

newcastle disease virus（NDV） can replicate and trigger autophagy in human tumor *** previous study confirmed the critical role of autophagy in NDV *** we studied the role of NDV structural proteins in the induction of autophagy through endoplasmic reticulum（ER） stress-related unfolded protein response（UPR） *** expression of the NDV nucleocapsid protein（NP） or phosphoprotein（P） was sufficient to induce *** or P expression also altered ER *** PERK and ATF6 pathways,but not the XBP1 pathway,all of which are components of the UPR,were activated in both NDV-infected and NP or P-transfected *** of PERK or ATF6 inhibited NDV-induced autophagy and reduced the extent of NDV ***,these data suggest not only roles for the NDV NP and P proteins in autophagy,but also offer new insights into the mechanisms of NDV-induced autophagy through activation of the ER stress-related UPR pathway.

关键词： Autophagy endoplasmic reticulum(ER) stress newcastle disease virus unfolded protein response(UPR)

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