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Fulltext Viral persistence in colorectal cancer cells infected by Newcastle disease virus

Chia SL, Yusoff K, Shafee N

Virol J, 2014 May 16;11:91.
PMID: 24886301 DOI: 10.1186/1743-422X-11-91

BACKGROUND: Newcastle disease virus (NDV), a single-stranded RNA virus of the family Paramyxoviridae, is a candidate virotherapy agent in cancer treatment. Promising responses were observed in clinical studies. Despite its high potential, the possibility of the virus to develop a persistent form of infection in cancer cells has not been investigated. Occurrence of persistent infection by NDV in cancer cells may cause the cells to be less susceptible to the virus killing. This would give rise to a population of cancer cells that remains viable and resistant to treatment.
RESULTS: During infection experiment in a series of colorectal cancer cell lines, we adventitiously observed a development of persistent infection by NDV in SW480 cells, but not in other cell lines tested. This cell population, designated as SW480P, showed resistancy towards NDV killing in a re-infection experiment. The SW480P cells retained NDV genome and produced virus progeny with reduced plaque forming ability.
CONCLUSION: These observations showed that NDV could develop persistent infection in cancer cells and this factor needs to be taken into consideration when using NDV in clinical settings.

Matched MeSH terms: Newcastle disease virus/growth & development*
Novel peptides that inhibit the propagation of Newcastle disease virus

Ramanujam P, Tan WS, Nathan S, Yusoff K

Arch Virol, 2002 May;147(5):981-93.
PMID: 12021868

A disulfide constrained random heptapeptide library displayed on filamentous bacteriophage M13 was applied to select specific ligands that interact with Newcastle disease virus (NDV). A fusion phage carrying the amino acid sequence TLTTKLY was selected from the panning procedure. An antibody competition assay showed that the selected phage was capable of competing with the polyclonal antibodies raised against NDV for binding sites on the virus. Determination of the binding affinity of this phage with NDV by an equilibrium binding assay in solution revealed two different dissociation constants, suggesting that there could be two distinct binding sites for the phage on NDV. Synthetic peptides with the sequence CTLTTKLYC, either in linear or cyclic conformations inhibited the binding of phage bearing the same sequence to NDV. These peptides also inhibited the hemolytic activity of the virus as well as its propagation in embryonated chicken eggs.

Matched MeSH terms: Newcastle disease virus/growth & development
Newcastle disease virus Malaysian strain AF2240 induces apoptosis in MCF-7 human breast carcinoma cells at an early stage of the virus life cycle

Ghrici M, El Zowalaty M, Omar AR, Ideris A

Int J Mol Med, 2013 Mar;31(3):525-32.
PMID: 23337979 DOI: 10.3892/ijmm.2013.1244

Newcastle disease virus (NDV) AF2240 Malaysian strain is a very virulent avian virus. NDV strain AF2240 was previously demonstrated to induce apoptosis in human breast carcinoma MCF-7 cells. However, at which stage of the NDV life cycle apoptosis is induced and whether NDV replication and protein synthesis are involved in apoptosis induction have yet to be determined. In the present study, we investigated the time course of NDV strain AF2240 nucleoprotein (NP) gene expression and the early apoptotic signs in the form of activation of caspase-8 and mitochondrial transition pore opening. In addition, the induction of apoptosis by both ultraviolet-inactivated and cycloheximide-treated NDV-infected MCF-7 cells were examined. Our findings showed that NDV strain AF2240 induced apoptosis at 1 h post-infection (pi) through activation of mitochondrial transition pore opening and at 2 h through activation of caspase-8, while the NP gene was expressed at 6 h pi. The induced apoptosis was independent of both virus replication and protein synthesis. In conclusion, NDV strain AF2240 induces apoptosis at an early stage of its life cycle, possibly during virus binding or fusion with the cell membrane. The mitochondrial-related pathway may be the central activator in NDV strain AF2240-induced apoptosis.

Matched MeSH terms: Newcastle disease virus/growth & development*
Fulltext Production of Newcastle disease virus by Vero cells grown on cytodex 1 microcarriers in a 2-litre stirred tank bioreactor

Arifin MA, Mel M, Abdul Karim MI, Ideris A

J Biomed Biotechnol, 2010;2010:586363.
PMID: 20625497 DOI: 10.1155/2010/586363

The aim of this study is to prepare a model for the production of Newcastle disease virus (NDV) lentogenic F strain using cell culture in bioreactor for live attenuated vaccine preparation. In this study, firstly we investigated the growth of Vero cells in several culture media. The maximum cell number was yielded by culture of Vero cells in Dulbecco's Modified Eagle Medium (DMEM) which was 1.93 x 10(6) cells/ml. Secondly Vero cells were grown in two-litre stirred tank bioreactor by using several commercial microcarriers. We achieved the maximum cell concentration about 7.95 x 10(5) cells/ml when using Cytodex 1. Later we produced Newcastle Disease virus in stirred tank bioreactor based on the design developed using Taguchi L4 method. Results reveal that higher multiplicity of infection (MOI) and size of cell inoculums can yield higher virus titer. Finally, virus samples were purified using high-speed centrifugation based on 3( * *)(3-1) Fractional Factorial Design. Statistical analysis showed that the maximum virus titer can be achieved at virus sample concentration of 58.45% (v/v), centrifugation speed of 13729 rpm, and centrifugation time of 4 hours. As a conclusion, high yield of virus titer could be achieved through optimization of cell culture in bioreactor and separation by high-speed centrifugation.

Matched MeSH terms: Newcastle disease virus/growth & development*
Fulltext Induction of apoptosis in MCF-7 cells by the hemagglutinin-neuraminidase glycoprotein of Newcastle disease virus Malaysian strain AF2240

Ghrici M, El Zowalaty M, Omar AR, Ideris A

Oncol Rep, 2013 Sep;30(3):1035-44.
PMID: 23807159 DOI: 10.3892/or.2013.2573

Newcastle disease virus (NDV) exerts its naturally occurring oncolysis possibly through the induction of apoptosis. We hypothesized that the binding of the virus to the cell via the hemagglutinin-neuraminidase (HN) glycoprotein may be sufficient to not only induce apoptosis but to induce a higher apoptosis level than the parental NDV AF2240 virus. NDV AF2240 induction of apoptosis in MCF-7 human breast cancer cells was analyzed and quantified. In addition, the complete HN gene of NDV strain AF2240 was amplified, sequenced and cloned into the pDisplay eukaryotic expression vector. HN gene expression was first detected at the cell surface membrane of the transfected MCF-7 cells. HN induction of apoptosis in transfected MCF-7 cells was analyzed and quantified. The expression of the HN gene alone was able to induce apoptosis in MCF-7 cells but it was a less potent apoptosis inducer compared to the parental NDV AF2240 strain. In conclusion, the NDV AF2240 strain is a more suitable antitumor candidate agent than its recombinant HN gene unless the latter is further improved by additional modifications.

Matched MeSH terms: Newcastle disease virus/growth & development
Human renal carcinoma cells respond to Newcastle disease virus infection through activation of the p38 MAPK/NF-κB/IκBα pathway

Ch'ng WC, Abd-Aziz N, Ong MH, Stanbridge EJ, Shafee N

Cell Oncol (Dordr), 2015 Aug;38(4):279-88.
PMID: 25930675 DOI: 10.1007/s13402-015-0229-5

Newcastle disease virus (NDV) is an oncolytic virus that is known to have a higher preference to cancer cells than to normal cells. It has been proposed that this higher preference may be due to defects in the interferon (IFN) responses of cancer cells. The exact mechanism underlying this process, however, remains to be resolved. In the present study, we examined the antiviral response towards NDV infection of clear cell renal cell carcinoma (ccRCC) cells. ccRCC is associated with mutations of the von Hippel-Lindau tumor suppressor gene VHL, whose protein product is important for eliciting cellular responses to changes in oxygen levels. The most common first line treatment strategy of ccRCC includes IFN. Unfortunately, most ccRCC cases are diagnosed at a late stage and often are resistant to IFN-based therapies. Alternative treatment approaches, including virotherapy using oncolytic viruses, are currently being investigated. The present study was designed to investigate the mechanistic pathways underlying the response of ccRCC cells to oncolytic NDV infection.

Matched MeSH terms: Newcastle disease virus/growth & development*