Newcastle Disease Virus V Protein Promotes Viral Replication in HeLa Cells through the Activation of MEK/ERK Signaling

Chu, Zhili; Ma, Jian-Gang; Wang, Caiying; Lu, Kejia; Li, Xiaoqin; Liu, Haijin; Wang, Xinglong; Xiao, Sa; Yang, Zhicong

doi:10.3390/v10090489

Cited by 16 publications

(10 citation statements)

References 51 publications

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“…Activation of the MEK/ERK signaling pathway has been observed as a positive factor in promoting viral replication in cells during various viral infections (Albarnaz et al, 2014; Shi et al, 2014; Takahashi and Suzuki, 2015). In previous findings, the MEK/ERK signaling pathway activity could facilitate NDV replication, and V protein played a vital role in activating the pathway (Chu et al, 2018). We therefore doubted whether MEK/ERK was involved in the induction of SOCS3 during NDV infection.…”

Section: Discussionmentioning

confidence: 88%

Newcastle Disease Virus Nonstructural V Protein Upregulates SOCS3 Expression to Facilitate Viral Replication Depending on the MEK/ERK Pathway

Wang

Jia

Ren

et al. 2019

Front. Cell. Infect. Microbiol.

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Newcastle disease virus (NDV) causes serious economic losses to the poultry industry. In our previous study, we found that NDV induced a strong innate immune response in the chicken embryo and bursa of Fabricius (BF). However, the underlying mechanisms by which NDV escapes the host innate immunity are not well-understood. The suppressor of cytokine signaling 3 (SOCS3) inhibits the type I interferon-dependent antiviral signaling pathway by utilizing a feedback loop. In this study, we analyzed the transcriptome data of the chicken embryo and BF infected with NDV and found significant upregulation of SOCS3. Next, we demonstrated that NDV infection and nonstructural V protein induced the up-regulation of SOCS3. Furthermore, we showed that overexpression of SOCS3 facilitated viral replication and reduced the expression of phosphorylation STAT1, MX1, and OASL, while inhibition of SOCS3 with siRNAs reduced virus replication and promoted the expression of phosphorylation STAT1, MX1, and OASL. Finally, we demonstrated that the MEK/ERK signaling pathway was involved in the expression of SOCS3 mediated by NDV infection and V protein transfection, and using specific inhibitor U0126 to block this signaling pathway attenuated SOCS3 expression and inhibited NDV replication through promoting the expression of type I interferon, OASL and MX1. Taken together, these data demonstrate that NDV infection and NDV nonstructural V protein activates the expression of SOCS3 at the mRNA and protein level through a mechanism dependent on the MEK/ERK signaling pathway, which benefits virus replication.

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Section: Discussionmentioning

confidence: 88%

Newcastle Disease Virus Nonstructural V Protein Upregulates SOCS3 Expression to Facilitate Viral Replication Depending on the MEK/ERK Pathway

Wang

Jia

Ren

et al. 2019

Front. Cell. Infect. Microbiol.

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“…The MEK/ERK signaling pathway regulates cancer cell proliferation, apoptosis, inflammation, angiogenesis, metastasis and drug resistance. In our previous work, we found that the V protein promotes viral replication in HeLa cells through the activation of the MEK/ERK signaling pathways [ 10 ]. Moreover, NDV selectively infects dividing cells and promotes viral proliferation [ 19 ], and these previous studies suggest that viral proteins may regulate viral replication by affecting cell proliferation.…”

Section: Discussionmentioning

confidence: 99%

“…In general, apoptosis of host cells can inhibit viral replication, and the V protein is known for its antiapoptotic activity [ 7 – 9 ]. In our previous study, we showed that the V protein can activate MEK/ERK signaling in HeLa cells [ 10 ]. Another study showed that the V protein can upregulate cytokine signaling 3 expression, and cytokine signaling 3 overexpression in chicken embryo fibroblast cells can activate the MEK/ERK signaling pathway [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

The V protein in oncolytic Newcastle disease virus promotes HepG2 hepatoma cell proliferation at the single-cell level

Chu

Yang

et al. 2023

BMC Cancer

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Background Newcastle disease virus (NDV) is an oncolytic virus that can inhibit cancer cell proliferation and kill cancer cells. The NDV nonstructural V protein can regulate viral replication; however, whether the V protein contributes to NDV oncolysis is unclear. Results This study revealed that NDV inhibited tumor cell proliferation and that V protein expression promoted the proliferation of HepG2 cells, as determined at the single-cell level. In addition, to identify the regulatory mechanism of the V protein in HepG2 cells, transcriptome sequencing was performed and indicated that the expression/activation of multiple cell proliferation-related genes/signaling pathways were changed in cells overexpressing the V protein. Hence, the MAPK and WNT signaling pathways were selected for verification, and after blocking these two signaling pathways with inhibitors, the V protein promotion of cell proliferation was found to be attenuated. Conclusions The results showed that the V protein regulated the proliferation of cancer cells through multiple signaling pathways, providing valuable references for future studies on the mechanism by which the V protein regulates cancer cell proliferation.

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“…The V protein, as a non-structural protein, is thought to be an interferon antagonist and is also associated with the virulence of NDV viruses [9]. Recent studies have shown that the V protein can mediate the promotion of NDV replication by participating in the ERK signalling pathway [10], while M is related to virus assembly and germination [11,12].…”

Section: Ivyspring International Publishermentioning

confidence: 99%

Advances in the Study of Antitumour Immunotherapy for Newcastle Disease Virus

Meng¹,

He²,

Zhong³

et al. 2021

Int. J. Med. Sci.

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This article reviews the preclinical research, clinical application and development of Newcastle disease virus (NDV) in the field of cancer therapy. Based on the distinctive antitumour properties of NDV and its positive interaction with the patient's immune system, this biologic could be considered a major breakthrough in cancer treatment. On one hand, NDV infection creates an inflammatory environment in the tumour microenvironment, which can directly activate NK cells, monocytes, macrophages and dendritic cells and promote the recruitment of immune cells. On the other hand, NDV can induce the upregulation of immune checkpoint molecules, which may break immune tolerance and immune checkpoint blockade resistance. In fact, clinical data have shown that NDV combined with immune checkpoint blockade can effectively enhance the antitumour response, leading to the regression of local tumours and distant tumours when injected, and this effect is further enhanced by targeted manipulation and modification of the NDV genome. At present, recombinant NDV and recombinant NDV combined with immune checkpoint blockers have entered different stages of clinical trials. Based on these studies, further research on NDV is warranted.

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Newcastle Disease Virus V Protein Promotes Viral Replication in HeLa Cells through the Activation of MEK/ERK Signaling

Cited by 16 publications

References 51 publications

Newcastle Disease Virus Nonstructural V Protein Upregulates SOCS3 Expression to Facilitate Viral Replication Depending on the MEK/ERK Pathway

Newcastle Disease Virus Nonstructural V Protein Upregulates SOCS3 Expression to Facilitate Viral Replication Depending on the MEK/ERK Pathway

The V protein in oncolytic Newcastle disease virus promotes HepG2 hepatoma cell proliferation at the single-cell level

Advances in the Study of Antitumour Immunotherapy for Newcastle Disease Virus

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