HN protein of Newcastle disease virus causes apoptosis in chicken embryo fibroblast cells

Ravindra, P. V.; Tiwari, Ashok Kumar; Sharma, Bhaskar; Rajawat, Yogendra Singh; Ratta, Barkha; Palia, Sudesh Kumar; Sundaresan, Nagalingam R.; Chaturvedi, Uttara; Gangaplara, Arunakumar; Chindera, Kantaraja; Saxena, M.; Subudhi, P.K.; A, Rai; Chauhan, R.S.

doi:10.1007/s00705-008-0057-2

Cited by 43 publications

(39 citation statements)

References 24 publications

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“…(2). In recent years, although some aspects of NDV pathogenesis have been investigated, the factors that affect NDV replication in its host are still poorly understood (3)(4)(5).…”

mentioning

confidence: 99%

Autophagy Benefits the Replication of Newcastle Disease Virus in Chicken Cells and Tissues

Sun

Ding

et al. 2014

J Virol

102

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bNewcastle disease virus (NDV) is an important avian pathogen. We previously reported that NDV triggers autophagy in U251 glioma cells, resulting in enhanced virus replication. In this study, we investigated whether NDV triggers autophagy in chicken cells and tissues to enhance virus replication. We demonstrated that NDV infection induced steady-state autophagy in chickenderived DF-1 cells and in primary chicken embryo fibroblast (CEF) cells, evident through increased double-or single-membrane vesicles, the accumulation of green fluorescent protein (GFP)-LC3 dots, and the conversion of LC3-I to LC3-II. In addition, we measured autophagic flux by monitoring p62/SQSTM1 degradation, LC3-II turnover, and GFP-LC3 lysosomal delivery and proteolysis, to confirm that NDV infection induced the complete autophagic process. Inhibition of autophagy by pharmacological inhibitors and RNA interference reduced virus replication, indicating an important role for autophagy in NDV infection. Furthermore, we conducted in vivo experiments and observed the conversion of LC3-I to LC3-II in heart, liver, spleen, lung, and kidney of NDV-infected chickens. Regulation of the induction of autophagy with wortmannin, chloroquine, or starvation treatment affects NDV production and pathogenesis in tissues of both lung and intestine; however, treatment with rapamycin, an autophagy inducer of mammalian cells, showed no detectable changes in chicken cells and tissues. Moreover, administration of the autophagy inhibitor wortmannin increased the survival rate of NDV-infected chickens. Our studies provide strong evidence that NDV infection induces autophagy which benefits NDV replication in chicken cells and tissues.

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“…(2). In recent years, although some aspects of NDV pathogenesis have been investigated, the factors that affect NDV replication in its host are still poorly understood (3)(4)(5).…”

mentioning

confidence: 99%

Autophagy Benefits the Replication of Newcastle Disease Virus in Chicken Cells and Tissues

Sun

Ding

et al. 2014

J Virol

102

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“…In our previous studies, we showed that the HN protein can cause apoptosis in chicken embryo fibroblasts and in HeLa cells [14,21]. We have demonstrated the activation of the SAPK/JNK pathway by HN [13].…”

Section: Discussionmentioning

confidence: 92%

“…The results showed a significant decrease in mitochondrial membrane potential in HN ? TNF-a-transfected HeLa cells at 48 h p.t., confirming the loss of mitochondrial membrane potential, which is an upstream event occurring during the mitochondrial pathway of apoptosis [14]. The loss of mitochondrial membrane potential leads to an efflux of cytochrome-c from the intermembrane space of mitochondria to the cytoplasm and initiates formation of the apoptosome, resulting in the proteolytic activation of the initiator caspase-9.…”

Section: Discussionmentioning

confidence: 99%

“…Newcastle disease virus (NDV) has inherent oncolytic properties because its multifunctional protein HN specifically activates the apoptotic machinery of tumor cells by upregulating the expression of ''TNF-related apoptosis-inducing ligand'' (TRAIL) and interferon-a [11][12][13]. HN protein has been shown to induce apoptosis in chicken embryo fibroblast (CEF) cells [14], human hepatoma SMMC-7721 cells [11], and MCF-7 cells [15]. Further, the expression of HN protein has been shown not only to reduce tumor growth but also to stimulate an innate anti-tumor response in a mouse model [16].…”

Section: Introductionmentioning

confidence: 99%

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HN protein of Newcastle disease virus sensitizes HeLa cells to TNF-α-induced apoptosis by downregulating NF-κB expression

et al. 2016

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Newcastle disease virus (NDV) is an oncolytic virus which selectively replicates in tumor cells and exerts anti-tumor cytotoxic activity by promoting cell death. In this study, we focus on characterization of the underlying mechanisms of NDV-induced cell death in HeLa cells. We find that NDV Herts/33 strain triggers both extrinsic and intrinsic apoptosis at late infection times. The activation of NF-кB pathway and subsequent up-regulation of TNF-α/TRAIL initiates extrinsic apoptosis, leading to activation of caspase 8 and cleavage of Bid into tBid. tBid transmits the extrinsic apoptotic signals to mitochondria and mediates intrinsic apoptosis, which is hallmarked by cleavage of caspase 9. Moreover, RIP1 is cleaved into RIP1-N and RIP1-C at D324 by caspase 8, and this cleavage promotes apoptosis. Surprisingly, over expression of RIP1 reduces apoptosis and depletion of RIP1 promotes apoptosis, suggesting full length RIP1 is anti-apoptotic. Moreover, necroptosis hallmark protein MLKL is activated by phosphorylation at 12-24 h.p.i., and RIP1 regulates the level of phosphor-MLKL. Immunostaining shows that RIP1 aggregates to stress granules (SGs) at 8-24 h.p.i., and phosphor-MLKL is also recruited to SGs, instead of migrating to plasma membrane to exert its necrotic function. Immunoprecipitation study demonstrates that RIP1 bind to phosphor-MLKL, and depletion of RIP1 reduces the aggregation of MLKL to SGs, suggesting that RIP1 recruits MLKL to SGs. Altogether, NDV infection initiates extrinsic apoptosis via activation of NF-кB and secretion of TNF-α/TRAIL. Activation of caspase 8 by TNF-α/TRAIL and subsequent cleavage of Bid and RIP1 transmit the death signals to mitochondria. Meanwhile, virus subverts the host defensive necroptosis via recruiting phosphor-MLKL by RIP1 to SGs. Thus, RIP1 is a central signaling protein in regulation of apoptosis and necroptosis during NDV infection. www.impactjournals.com/oncotarget/

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“…Induction of apoptosis by NDV requires viral entry, replication, de-novo protein synthesis, and activation of caspases. In addition to its direct cytopathic effects, the anti-cancer activity of NDV is associated with the activation of both innate and adaptive immune responses [51].…”

Section: Newcastle Disease Virus (Ndv)mentioning

confidence: 99%

An Overview on Oncolytic Viruses as Cancer Therapy

Demisse¹

2017

IJCR

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HN protein of Newcastle disease virus causes apoptosis in chicken embryo fibroblast cells

Cited by 43 publications

References 24 publications

Autophagy Benefits the Replication of Newcastle Disease Virus in Chicken Cells and Tissues

Autophagy Benefits the Replication of Newcastle Disease Virus in Chicken Cells and Tissues

HN protein of Newcastle disease virus sensitizes HeLa cells to TNF-α-induced apoptosis by downregulating NF-κB expression

An Overview on Oncolytic Viruses as Cancer Therapy

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