Accidental persistent infection of cell lines by Newcastle disease virus, showing three unusual features ? Defective neuraminidase, temperature sensitivity and intranuclear inclusions

1976 ◽  
Vol 50 (1-2) ◽  
pp. 147-157 ◽  
Author(s):  
G. Fraser ◽  
Helen H. Edwards ◽  
M. S. McNulty ◽  
J. M. S. Ruben
Keyword(s):  
Newcastle Disease Virus ◽  
Disease Virus ◽  
Cell Lines ◽  
Temperature Sensitivity ◽  
Newcastle Disease ◽  
Persistent Infection ◽  
Intranuclear Inclusions

scholarly journals Persistent Newcastle disease virus infection in bladder cancer cells is associated with putative pro-survival and anti-viral transcriptomic changes

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Lee-Chin Chan ◽  
Jeevanathan Kalyanasundram ◽  
Sze-Wei Leong ◽  
Mas Jaffri Masarudin ◽  
Abhi Veerakumarasivam ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Newcastle Disease Virus ◽  
Cancer Cells ◽  
Disease Virus ◽  
Newcastle Disease ◽  
Persistent Infection ◽  
Signalling Pathways ◽  
Bladder Cancer Cells ◽  
Transcriptomic Changes

Abstract Background Newcastle disease virus (NDV) is an oncolytic virus with excellent selectivity against cancer cells, both in vitro and in vivo. Unfortunately, prolonged in vitro NDV infection results in the development of persistent infection in the cancer cells which are then able to resist NDV-mediated oncolysis. However, the mechanism of persistency of infection remains poorly understood. Methods In this study, we established persistently NDV-infected EJ28 bladder cancer cells, designated as EJ28P. Global transcriptomic analysis was subsequently carried out by microarray analysis. Differentially expressed genes (DEGs) between EJ28 and EJ28P cells identified by the edgeR program were further analysed by Gene Set Enrichment Analysis (GSEA) and Ingenuity Pathway Analysis (IPA) analyses. In addition, the microarray data were validated by RT-qPCR. Results Persistently NDV-infected EJ28 bladder cancer cells were successfully established and confirmed by flow cytometry. Microarray analysis identified a total of 368 genes as differentially expressed in EJ28P cells when compared to the non-infected EJ28 cells. GSEA revealed that the Wnt/β-catenin and KRAS signalling pathways were upregulated while the TGF-β signalling pathway was downregulated. Findings from this study suggest that the upregulation of genes that are associated with cell growth, pro-survival, and anti-apoptosis may explain the survivability of EJ28P cells and the development of persistent infection of NDV. Conclusions This study provides insights into the transcriptomic changes that occur and the specific signalling pathways that are potentially involved in the development and maintenance of NDV persistency of infection in bladder cancer cells. These findings warrant further investigation and is crucial towards the development of effective NDV oncolytic therapy against cancer.

scholarly journals Newcastle Disease Virus Establishes Persistent Infection in Tumor Cells In Vitro: Contribution of the Cleavage Site of Fusion Protein and Second Sialic Acid Binding Site of Hemagglutinin-Neuraminidase

2017 ◽  
Vol 91 (16) ◽  
Author(s):  
Udaya S. Rangaswamy ◽  
Weijia Wang ◽  
Xing Cheng ◽  
Patrick McTamney ◽  
Danielle Carroll ◽  
...  
Keyword(s):  
Newcastle Disease Virus ◽  
Disease Virus ◽  
Receptor Binding ◽  
Newcastle Disease ◽  
Persistent Infection ◽  
Cleavage Site ◽  
Protein Cleavage ◽  
F Protein ◽  
Sialic Acid Binding

ABSTRACT Newcastle disease virus (NDV) is an oncolytic virus being developed for the treatment of cancer. Following infection of a human ovarian cancer cell line (OVCAR3) with a recombinant low-pathogenic NDV, persistent infection was established in a subset of tumor cells. Persistently infected (PI) cells exhibited resistance to superinfection with NDV and established an antiviral state, as demonstrated by upregulation of interferon and interferon-induced genes such as myxoma resistance gene 1 (Mx1) and retinoic acid-inducing gene-I (RIG-I). Viruses released from PI cells induced higher cell-to-cell fusion than the parental virus following infection in two tumor cell lines tested, HT1080 and HeLa, and remained attenuated in chickens. Two mutations, one in the fusion (F) protein cleavage site, F117S (F117S), and another in hemagglutinin-neuraminidase (HN), G169R (HN169R), located in the second sialic acid binding region, were responsible for the hyperfusogenic phenotype. F117S improves F protein cleavage efficiency, facilitating cell-to-cell fusion, while HN169R possesses a multifaceted role in contributing to higher fusion, reduced receptor binding, and lower neuraminidase activity, which together result in increased fusion and reduced viral replication. Thus, establishment of persistent infection in vitro involves viral genetic changes that facilitate efficient viral spread from cell to cell as a potential mechanism to escape host antiviral responses. The results of our study also demonstrate a critical role in the viral life cycle for the second receptor binding region of the HN protein, which is conserved in several paramyxoviruses. IMPORTANCE Oncolytic Newcastle disease virus (NDV) could establish persistent infection in a tumor cell line, resulting in a steady antiviral state reflected by constitutively expressed interferon. Viruses isolated from persistently infected cells are highly fusogenic, and this phenotype has been mapped to two mutations, one each in the fusion (F) and hemagglutinin-neuraminidase (HN) proteins. The F117S mutation in the F protein cleavage site improved F protein cleavage efficiency while the HN169R mutation located at the second receptor binding site of the HN protein contributed to a complex phenotype consisting of a modest increase in fusion and cell killing, lower neuraminidase activity, and reduced viral growth. This study highlights the intricate nature of these two mutations in the glycoproteins of NDV in the establishment of persistent infection. The data also shed light on the critical balance between the F and HN proteins required for efficient NDV infection and their role in avian pathogenicity.

scholarly journals Analysis of PPI networks of transcriptomic expression identifies hub genes associated with Newcastle disease virus persistent infection in bladder cancer

2020 ◽  
Author(s):  
Umar Ahmad ◽  
De Ming Chau ◽  
Suet Lin Chia ◽  
Khatijah Yusoff ◽  
Syahril Abdullah ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Newcastle Disease Virus ◽  
Cancer Cells ◽  
Disease Virus ◽  
Newcastle Disease ◽  
Persistent Infection ◽  
Ppi Network ◽  
Hub Genes ◽  
Persistently Infected ◽  
Bladder Cancer Cells

AbstractMotivationBladder cancer cells acquire persistent infection associated with oncolytic Newcastle disease virus (NDV) in which its molecular events are still unclear. This poses a potential problem for oncolytic virus application for cancer therapy. To unravel the molecular mechanism underlying the development of NDV persistent infection in bladder cancer, we used mRNA expression profile of the persistently infected bladder cancer cells to construct PPI network.ResultsBased on path and module exploring in the PPI network, the bridges were found mainly from pathways of p53 signalling, ECM-receptor interaction, and TGF-beta signalling by the upregulated mRNAs, to the antigen processing and presentation, protein processing in endoplasmic reticulum, completement and coagulation cascades by the downregulated mRNAs in NDV persistent TCCSUPPi cells. In persistent EJ28Pi cells comparatively, connections were identified mainly from pathways of renal carcinoma, viral carcinogenesis, Ras signalling and cell cycle by the upregulated mRNAs, to the Wnt signalling, HTLV-I infection and pathways in cancer by the downregulated mRNAs. This connection was mainly dependent on of RPL8- HSPA1A/HSPA4 in TCCSUPPi cells and EP300, PTPN11, RAC1 - TP53, SP1, CCND1 and XPO1 in EJ28Pi cells. Oncomine validation showed that the top hub genes identified in the network that includes RPL8, THBS1, F2 from TCCSUPPi and TP53 and RAC1 from EJ28Pi are involved in the development and progression of bladder cancer. Protein-drug interaction network, have identified several drugs targets that could be used to disconnect the linkages between modules and prevent bladder cancer cells from acquiring NDV persistent infection. This is the first time reporting the PPI network analysis of differentially expressed mRNAs of the NDV persistently infected bladder cancer cell lines which provide an insight into screening drugs that could be used together with NDV to manage bladder cancer resistance to therapy and progression.

scholarly journals Decreased Dependence on Receptor Recognition for the Fusion Promotion Activity of L289A-Mutated Newcastle Disease Virus Fusion Protein Correlates with a Monoclonal Antibody-Detected Conformational Change

2005 ◽  
Vol 79 (2) ◽  
pp. 1180-1190 ◽  
Author(s):  
Jianrong Li ◽  
Vanessa R. Melanson ◽  
Anne M. Mirza ◽  
Ronald M. Iorio
Keyword(s):  
Newcastle Disease Virus ◽  
Conformational Change ◽  
Disease Virus ◽  
Cell Lines ◽  
Newcastle Disease ◽  
Energy Requirement ◽  
Target Cells ◽  
F Protein ◽  
Viral Hemagglutinin ◽  
Receptor Recognition

ABSTRACT It has been shown that the L289A-mutated Newcastle disease virus (NDV) fusion (F) protein gains the ability to promote fusion of Cos-7 cells independent of the viral hemagglutinin-neuraminidase (HN) protein and exhibits a 50% enhancement in HN-dependent fusion over wild-type (wt) F protein. Here, we show that HN-independent fusion by L289A-F is not exhibited in BHK cells or in several other cell lines. However, similar to the results in Cos-7 cells, the mutated protein plus HN does promote 50 to 70% more fusion above wt levels in all of the cell lines tested. L289A-F protein exhibits the same specificity as the wt F protein for the homologous HN protein, as well as NDV-human parainfluenza virus 3 HN chimeras. The mutated F protein promotes fusion more effectively than the wt when it is coexpressed with either the chimeras or HN proteins deficient in receptor recognition activity. In addition, its fusogenic activity is significantly more resistant to removal of sialic acid on target cells. These findings are consistent with the demonstration that L289A-F interacts more efficiently with wt and mutated HN proteins than does wt F by a cell surface coimmunoprecipitation assay. Taken together, these findings indicate that L289A-F promotes fusion by a mechanism analogous to that of the wt protein with respect to the HN-F interaction but is less dependent on the attachment activity of HN. The phenotype of the mutated F protein correlates with a conformational change in the protein detectable by two different monoclonal antibodies. This conformational change may reflect a destabilization of F structure induced by the L289A substitution, which may in turn indicate a lower energy requirement for fusion activation.

Intranuclear Inclusions in Cells Infected with Newcastle Disease Virus

1999 ◽  
Vol 46 (6) ◽  
pp. 411-421 ◽  
Author(s):  
H. Granzow ◽  
F. Weiland ◽  
E. Mundt ◽  
B. K ◽  
. ollner ◽  
...  
Keyword(s):  
Newcastle Disease Virus ◽  
Disease Virus ◽  
Newcastle Disease ◽  
Intranuclear Inclusions ◽  
In Cells
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