Analysis of Three Properties of Newcastle Disease Virus for Fighting Cancer: Tumor-Selective Replication, Antitumor Cyto
Newcastle disease virus (NDV), a bird paramyxovirus, is an antitumor agent which has shown benefits to cancer patients. Its antineoplastic efficacy appears to be associated with three properties of the virus: 1. Selective replication in tumor cells. This
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et al. (eds.), Oncolytic Viruses: Methods and Protocols, Methods in Molecular Biology, vol. 797, DOI 10.1007/978-1-61779-340-0_13, © Springer Science+Business Media, LLC 2012
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List of Abbreviations D-SMA A490 ATV-NDV BSA cDNA CT ELISA ELISPOT ER HN HSC HU IFN IRF-3 IRF-7 MOI NDV pAb PBMC PBS PCR PHA RIG-I rpm RPNI RT-PCR SDS STAT Tet TGI TNA UV
D-Smooth muscle actin Absorbance at 490 nm Autologous tumor vaccine with NDV Bovin serum albumin Complementary DNA Threshold cycle Enzyme-linked immunosorbent assay Enzyme-linked immunosorbent spot Endoplasmic reticulum Hemagglutinin protein of NDV Hepatic stellate cell Hemagglutination unit Interferon Interferon regulatory factor 3 Interferon regulatory factor 7 Multiplicity of infection Newcastle disease virus Polyclonal antibodies Peripheral blood mononuclear cell Phosphate-buffered saline Polymerase chain reaction Phytohemagglutinin Retinoic acid-inducible gene I Rotation per minute Roswell park memorial institute medium Real-time PCR Sodium dodecyl sulfate Signal transducers and activation of transcription Tetracycline Tumor growth inhibition Tumor-neutralization assay Ultraviolet
1. Introduction Although Newcastle disease virus (NDV) can induce fatal respiratory diseases in birds (e.g., chicken pest), this avian paramyxovirus is not a human pathogen (1, 2). NDV is an enveloped virus of 100–300-nm diameter with a negative-sense single-stranded RNA genome of roughly 16,000 nucleotides. This viral RNA contains six genes encoding six major polypeptides, among them two surface proteins: the hemagglutinin– neuraminidase (HN) protein (74 kDa) and the fusion (F) protein (67 kDa). These two proteins are involved during NDV infection,
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respectively, in the binding of the virus to a host cell’s surface via ubiquitously expressed sialic acid containing receptors and in the fusion of the viral and the host cell membrane. This membrane fusion event allows the viral genome to enter the cytoplasm of the host cell. It is important to mention that this viral genome replicates only in the cytoplasm and, not having a DNA intermediate, virus-specific sequences do not integrate into the genome of the infected cell. At the beginning of viral infection, the negativestranded RNA genome is transcribed within the cytoplasm into messenger RNAs (positive) and translated to viral proteins (first step of viral infection). The nucleocapsid as “antigenome” is then used as a template for viral replication (second step of viral infection). This virus can then produce progeny particles that can eventually infect other cells. One main property which is important for classifying NDV viral strains is their virulence. They are either lytic and show, then, a capacity of multicylic replication in tumor cells. Or they are nonlytic and have a monocyclic replication pattern in tumor cells (3). There is a long history of the use of both types of NDV strains for treating cancer in man. Therefore, the
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