Differentially Regulated Interferon Response Determines the Outcome of Newcastle Disease Virus Infection in Normal and Tumor Cell Lines

Krishnamurthy, Sateesh; Takimoto, Toru; Scroggs, Ruth Ann; Portner, Allen

doi:10.1128/jvi.02618-05

Cited by 146 publications

(153 citation statements)

References 53 publications

(52 reference statements)

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“…Examples include vesicular stomatitis virus (VSV), Newcastle disease virus (NDV), myxoma virus and ICP0-null HSV-1 oncolytic vectors. [6][7][8][9] HSV-1 vectors have generated much interest in the field, as HSV-1 was the first virus used to show that a genetic mutation could render a virus oncolytic. To date, Phase I and II clinical trials have been conducted with various HSV-1 mutants, showing the safety of administering various oncolytic mutants of HSV-1 in humans.…”

Section: Introductionmentioning

confidence: 99%

Bovine herpesvirus type 1 as a novel oncolytic virus

2009

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Oncolytic virotherapy is a promising avenue of cancer gene therapy. Current vectors include human viruses that have been engineered to replicate in tumor cells or nonhuman viruses that are naturally oncotropic and preferentially replicate in tumor cells harboring defects in innate immune pathways such as the type 1 interferon (IFN) pathway. Bovine herpesvirus type 1 (BHV-1) is a species-specific herpesvirus closely related to the human herpes simplex virus type 1 (HSV-1). Although BHV-1 does not efficiently replicate in and affect cellular viability of normal human cells, it is capable of infecting and killing various immortalized and transformed human cell types. Surprisingly, BHV-1 infection of human cells fails to elicit IFN production at the mRNA or protein level and the ability of BHV-1 to kill immortalized and transformed human cells does not correlate with defects in IFN pathways. Furthermore, although some cross-reactivity between BHV-1 and HSV-1 exists, the majority of human antibody or serum samples tested failed to neutralize BHV-1 despite possessing HSV-1 neutralizing capacity. Thus, BHV-1 is a novel candidate oncolytic virus with a distinct mechanism of tumor targeting.

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Section: Introductionmentioning

confidence: 99%

Bovine herpesvirus type 1 as a novel oncolytic virus

2009

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“…The innate immune response to NDV infection relies primarily on the induction of the IFN response and related pathways (Cheng et al, 2014;Krishnamurthy et al, 2006;Susta et al, 2013). NDV also encounters a range of antiviral responses, which are proposed to depend on the protein kinase R (PKR)-induced PKR/eIF2a signalling cascade and sequestosome 1 (SQSTM1)-mediated selective degradation of mitochondria by autophagy, called 'mitophagy' (Meng et al, 2014;Zhang et al, 2014).…”

mentioning

confidence: 99%

Expression of Raf kinase inhibitor protein is downregulated in response to Newcastle disease virus infection to promote viral replication

Yin

Liu

et al. 2015

Journal of General Virology

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Newcastle disease virus (NDV) causes a severe and economically significant disease affecting almost the entire poultry industry worldwide. However, factors that affect NDV replication in host cells are poorly understood. Raf kinase inhibitory protein (RKIP) is a physiological inhibitor of c-RAF kinase and NF-kB signalling, known for their functions in the control of immune response as well as tumour invasion and metastasis. In the present study, we investigated the consequences of overexpression of host RKIP during viral infection. We demonstrate that NDV infection represses RKIP expression thereby promoting virus replication. Experimental upregulation of RKIP in turn acts as a potential antiviral defence mechanism in host cells that restricts NDV replication by repressing the activation of Raf/MEK/ERK and IkBa/NF-kB signalling pathways. Our results not only extend the concept of linking NDV-host interactions, but also reveal RKIP as a new class of protein-kinase-inhibitor protein that affects NDV replication with therapeutic potential.

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“…17 NDV, an avian virus, may represent a different example of oncolytic virus as its V gene product, that is known to counteract IFN response in avian cells, is completely inactive in mammalian cells. 39 Notwithstanding, the oncolytic effect of NDV was shown related to a deficient IFN system in one study 15 and conversely shown independent of the IFN system in yet another study. 19 To further investigate the role of the IFN system in the oncolytic mechanism of NDV-HUJ, we pretreated the cells with recombinant IFN-b and tested for replication and the oncolytic activities of the virus.…”

Section: Discussionmentioning

confidence: 97%

“…15,16 Such a defect results in higher viral replication in the tumor cells and consequently to the selective oncolysis. 17 NDV, an avian virus, may represent a different example of oncolytic virus as its V gene product, that is known to counteract IFN response in avian cells, is completely inactive in mammalian cells.…”

Section: Discussionmentioning

confidence: 99%

“…13,14 Several studies have attributed the selective oncolytic activity of some RNA viruses, including vesicular stomatitis virus (VSV) and NDV, to defects in the interferon (IFN) system, observed in many tumor cell lines. [15][16][17][18] As NDV is very sensitive to IFN, its replication was found to be inhibited in the IFN competent normal cells but not in the tumor cells that failed to develop a proper antiviral state. However, many tumor cells do not display defects in the IFN system yet still are selectively destroyed by NDV.…”

Section: Introductionmentioning

confidence: 99%

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Selective oncolytic effect of an attenuated Newcastle disease virus (NDV-HUJ) in lung tumors

et al. 2008

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Newcastle disease virus (NDV), an avian paramyxovirus, has a potential oncolytic effect that may be of significance in the treatment of a variety of cancer diseases. An attenuated lentogenic isolate of NDV (HUJ) demonstrated a selective cytopathic effect upon a panel of human and mouse lung tumor cells, as compared to human nontumorigenic lung cells. The virus-selective oncolytic effect is apoptosis dependent, and related to higher levels of viral transcription, translation and progeny virus formation. Furthermore, NDV-HUJ oncolytic activity is directed in-cis and not through induction of cytokines, that may act in-trans on neighboring cells. Development of primary lung tumors and of the consequent metastasis in mice inoculated with mouse lung tumor cells 3LL-D122 was decreased following treatment with NDV-HUJ. The preferential killing of the tumor cells is not due to a deficiency in the interferon (IFN) system, as expression of the IFN-b gene, in the infected cells, is properly induced. Moreover, pretreatment with IFN effectively protected the tumor cells from the virus oncolytic effect. We conclude therefore, that NDV-HUJ should have a significant benefit in the treatment of lung cancer as well as other malignancies.

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Differentially Regulated Interferon Response Determines the Outcome of Newcastle Disease Virus Infection in Normal and Tumor Cell Lines

Cited by 146 publications

References 53 publications

Bovine herpesvirus type 1 as a novel oncolytic virus

Bovine herpesvirus type 1 as a novel oncolytic virus

Expression of Raf kinase inhibitor protein is downregulated in response to Newcastle disease virus infection to promote viral replication

Selective oncolytic effect of an attenuated Newcastle disease virus (NDV-HUJ) in lung tumors

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