Newcastle disease virus degrades SIRT3 via PINK1-PRKN-dependent mitophagy to reprogram energy metabolism in infected cells

Gong, Yabin; Liu, Panrao; Sun, Yingjie; Lu, Shanxin; Liu, Weiwei; Tan, Lei; Chen, Song; Qiu, Xusheng; Liao, Ying; Yu, Shuang; Liu, Xiufan; Lin, Shuhai; Chen, Ding

doi:10.1080/15548627.2021.1990515

Cited by 74 publications

(52 citation statements)

References 78 publications

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“…Additionally, cell autophagy plays an important role in clearing intracellular substances and maintaining the stability of the intracellular environment ( 70 ), and this can also affect the life cycle of the virus by regulating cell metabolism. For example, NDV infection has been demonstrated to regulate host glucose metabolism through mitochondrial autophagy ( 71 ). Typically, lipids can be used as autophagy substrates.…”

Section: Discussionmentioning

confidence: 99%

Integrative Transcriptomics and Proteomics Analysis Provide a Deep Insight Into Bovine Viral Diarrhea Virus-Host Interactions During BVDV Infection

Wang

Jiang

et al. 2022

Front. Immunol.

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Bovine viral diarrhea virus (BVDV) is the causative agent of bovine viral diarrhea-mucosal disease (BVD-MD), an important viral disease in cattle that is responsible for extensive economic losses to the cattle industry worldwide. Currently, several underlying mechanisms involved in viral replication, pathogenesis, and evading host innate immunity of BVDV remain to be elucidated, particularly during the early stage of virus infection. To further explore the mechanisms of BVDV-host interactions, the transcriptomics and proteomics profiles of BVDV-infected MDBK cells were sequenced using RNA-seq and iTRAQ techniques, respectively, and followed by an integrative analysis. Compared with mock-infected MDBK cells, a total of 665 differentially expressed genes (DEGs) (391 down-regulated, 274 up-regulated) and 725 differentially expressed proteins (DEPs) (461 down-regulated, 264 up-regulated) were identified. Among these, several DEGs and DEPs were further verified using quantitative RT-PCR and western blot. Following gene ontology (GO) annotation and KEGG enrichment analysis, we determined that these DEGs and DEPs were significantly enriched in multiple important cellular signaling pathways including NOD-like receptor, Toll-like receptor, TNF, NF-κB, MAPK, cAMP, lysosome, protein processing in endoplasmic reticulum, lipid metabolism, and apoptosis signaling pathways. Significantly, the down-regulated DEGs and DEPs were predominantly associated with apoptosis-regulated elements, inflammatory factors, and antiviral elements that were involved in innate immunity, thus, indicating that BVDV could inhibit apoptosis and the expression of host antiviral genes to facilitate viral replication. Meanwhile, up-regulated DEGs and DEPs were primarily involved in metabolism and autophagy signaling pathways, indicating that BVDV could utilize the host metabolic resources and cell autophagy to promote replication. However, the potential mechanisms BVDV-host interactions required further experimental validation. Our data provide an overview of changes in transcriptomics and proteomics profiles of BVDV-infected MDBK cells, thus, providing an important basis for further exploring the mechanisms of BVDV-host interactions.

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Section: Discussionmentioning

confidence: 99%

Integrative Transcriptomics and Proteomics Analysis Provide a Deep Insight Into Bovine Viral Diarrhea Virus-Host Interactions During BVDV Infection

Wang

Jiang

et al. 2022

Front. Immunol.

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“…Avian Influenza Virus (AIV) and Newcastle Disease Virus (NDV) infections cause serious diseases in birds and pose major challenges to the global poultry industry ( Li et al, 2019 ; Gong et al, 2021 ). Investigating the antiviral targets against those pathogens will be helpful for the prevention of transmission of avian infectious diseases and solving public health issues.…”

Section: Introductionmentioning

confidence: 99%

A Role for the Chicken Interferon-Stimulated Gene CMPK2 in the Host Response Against Virus Infection

Feng

Liu

et al. 2022

Front. Microbiol.

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Virus infection can lead to the production of interferon, which activates the JAK/STAT pathway and induces the expression of multiple downstream interferon-stimulated genes (ISGs) to achieve their antiviral function. Cytidine/uridine monophosphate kinase 2 (CMPK2) gene has been identified as an ISG in human and fish, and is also known as a rate-limiting enzyme in mitochondria to maintain intracellular UTP/CTP levels, which is necessary for de novo mitochondrial DNA synthesis. By mining previous microarray data, it was found that both Avian Influenza Virus (AIV) and Newcastle Disease Virus (NDV) infection can lead to the significant upregulation of chicken CMPK2 gene. However, little is known about the function of CMPK2 gene in chickens. In the present study, the open reading frame (ORF) of chicken CMPK2 (chCMPK2) was cloned from DF-1, a chicken embryo fibroblasts cell line, and subjected to further analysis. Sequence analysis showed that chCMPK2 shared high similarity in amino acid with CMPK2 sequences from all the other species, especially reptiles. A thymidylate kinase (TMK) domain was identified in the C-terminus of chCMPK2, which is highly conserved among all species. In vitro, AIV infection induced significant increases in chCMPK2 expression in DF-1, HD11, and the chicken embryonic fibroblasts (CEF), while obvious increase only detected in DF-1 cells and CEF cells after NDV infection. In vivo, the expression levels of chCMPK2 were up-regulated in several tissues from AIV infected chickens, especially the brain, spleen, bursa, kidney, intestine, heart and thymus, and notable increase of chCMPK2 was detected in the bursa, kidney, duodenum, lung, heart, and thymus during NDV infection. Here, using MDA5 and IFN-β knockdown cells, we demonstrated that as a novel ISG, chCMPK2 could be regulated by the MDA5/IFN-β pathway. The high expression level of exogenous chCMPK2 displayed inhibitory effects on AIV and NDV as well as reduced viral RNA in infected cells. We further demonstrated that Asp135, a key site on the TMK catalytic domain, was identified as critical for the antiviral activities of chCMPK2. Taken together, these data demonstrated that chCMPK2 is involved in the chicken immune system and may play important roles in host anti-viral responses.

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“…The IBV Beaudette strain used in this study was adapted to DF-1, H1299 and Vero cells, and was a gift from Prof. Dingxiang Liu's laboratory (South China Agricultural University) (Wang et al, 2019;Gao et al, 2021). The culture of DF-1, Vero and H1299 cell lines was performed according to previously described methods in our laboratory (Wang et al, 2019;Gong et al, 2021), In brief, DF-1 and Vero cells were grown in Dulbecco's modified Eagle's medium with 10% fetal calf serum. H1299 cells were maintained in Roswell Park Memorial Institute 1640 medium supplemented with 10% (v/v) fetal calf serum.…”

Section: Cell Culture and Virusmentioning

confidence: 99%

Non-Targeted Metabolomic Analysis of Chicken Kidneys in Response to Coronavirus IBV Infection Under Stress Induced by Dexamethasone

Dai

Wang

Liao

et al. 2022

Front. Cell. Infect. Microbiol.

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Stress in poultry can lead to changes in body metabolism and immunity, which can increase susceptibility to infectious diseases. However, knowledge regarding chicken responses to viral infection under stress is limited. Dexamethasone (Dex) is a synthetic glucocorticoid similar to that secreted by animals under stress conditions, and has been widely used to induce stress in chickens. Herein, we established a stress model in 7-day-old chickens injected with Dex to elucidate the effects of stress on IBV replication in the kidneys. The metabolic changes, immune status and growth of the chickens under stress conditions were comprehensively evaluated. Furthermore, the metabolic profile, weight gain, viral load, serum cholesterol levels, cytokines and peripheral blood lymphocyte ratio were compared in chickens treated with Dex and infected with IBV. An LC-MS/MS-based metabolomics method was used to examine differentially enriched metabolites in the kidneys. A total of 113 metabolites whose abundance was altered after Dex treatment were identified, most of which were lipids and lipid-like molecules. The principal metabolic alterations in chicken kidneys caused by IBV infection included fatty acid, valine, leucine and isoleucine metabolism. Dex treatment before and after IBV infection mainly affected the host’s tryptophan, phenylalanine, amino sugar and nucleotide sugar metabolism. In addition, Dex led to up-regulation of serum cholesterol levels and renal viral load in chickens, and to the inhibition of weight gain, peripheral blood lymphocytes and IL-6 production. We also confirmed that the exogenous cholesterol in DF-1 cells promoted the replication of IBV. However, whether the increase in viral load in kidney tissue is associated with the up-regulation of cholesterol levels induced by Dex must be demonstrated in future experiments. In conclusion, chick growth and immune function were significantly inhibited by Dex. Host cholesterol metabolism and the response to IBV infection are regulated by Dex. This study provides valuable insights into the molecular regulatory mechanisms in poultry stress, and should support further research on the intrinsic link between cholesterol metabolism and IBV replication under stress conditions.

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Newcastle disease virus degrades SIRT3 via PINK1-PRKN-dependent mitophagy to reprogram energy metabolism in infected cells

Cited by 74 publications

References 78 publications

Integrative Transcriptomics and Proteomics Analysis Provide a Deep Insight Into Bovine Viral Diarrhea Virus-Host Interactions During BVDV Infection

Integrative Transcriptomics and Proteomics Analysis Provide a Deep Insight Into Bovine Viral Diarrhea Virus-Host Interactions During BVDV Infection

A Role for the Chicken Interferon-Stimulated Gene CMPK2 in the Host Response Against Virus Infection

Non-Targeted Metabolomic Analysis of Chicken Kidneys in Response to Coronavirus IBV Infection Under Stress Induced by Dexamethasone

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