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Viruses Mar 2023Newcastle disease (ND) has been a consistent risk factor to the poultry industry worldwide. Its pathogen, Newcastle disease virus (NDV), is also a promising antitumor... (Review)
Review
Newcastle disease (ND) has been a consistent risk factor to the poultry industry worldwide. Its pathogen, Newcastle disease virus (NDV), is also a promising antitumor treatment candidate. The pathogenic mechanism has intrigued the great curiosity of researchers, and advances in the last two decades have been summarized in this paper. The NDV's pathogenic ability is highly related to the basic protein structure of the virus, which is described in the Introduction of this review. The overall clinical signs and recent findings pertaining to NDV-related lymph tissue damage are then described. Given the involvement of cytokines in the overall virulence of NDV, cytokines, particularly IL6 and IFN expressed during infection, are reviewed. On the other hand, the host also has its way of antagonizing the virus, which starts with the detection of the pathogen. Thus, advances in NDV's physiological cell mechanism and the subsequent IFN response, autophagy, and apoptosis are summarized to provide a whole picture of the NDV infection process.
Topics: Animals; Newcastle disease virus; Newcastle Disease; Poultry; Cytokines; Chickens; Poultry Diseases
PubMed: 37112843
DOI: 10.3390/v15040864 -
Autophagy Jul 2022Lacking a self-contained metabolism network, viruses have evolved multiple mechanisms for rewiring the metabolic system of their host to hijack the host's metabolic...
Lacking a self-contained metabolism network, viruses have evolved multiple mechanisms for rewiring the metabolic system of their host to hijack the host's metabolic resources for replication. Newcastle disease virus (NDV) is a paramyxovirus, as an oncolytic virus currently being developed for cancer treatment. However, how NDV alters cellular metabolism is still far from fully understood. In this study, we show that NDV infection reprograms cell metabolism by increasing glucose utilization in the glycolytic pathway. Mechanistically, NDV induces mitochondrial damage, elevated mitochondrial reactive oxygen species (mROS) and ETC dysfunction. Infection of cells depletes nucleotide triphosphate levels, resulting in elevated AMP:ATP ratios, AMP-activated protein kinase (AMPK) phosphorylation, and MTOR crosstalk mediated autophagy. In a time-dependent manner, NDV shifts the balance of mitochondrial dynamics from fusion to fission. Subsequently, PINK1-PRKN-dependent mitophagy was activated, forming a ubiquitin chain with MFN2 (mitofusin 2), and molecular receptor SQSTM1/p62 recognized damaged mitochondria. We also found that NDV infection induces NAD-dependent deacetylase SIRT3 loss via mitophagy to engender HIF1A stabilization, leading to the switch from oxidative phosphorylation (OXPHOS) to aerobic glycolysis. Overall, these studies support a model that NDV modulates host cell metabolism through PINK1-PRKN-dependent mitophagy for degrading SIRT3. AMPK: AMP-activated protein kinase; CCCP: carbonyl cyanide 3-chlorophenylhydrazone; ECAR: extracellular acidification rate; hpi: hours post infection LC-MS: liquid chromatography-mass spectrometry; mito-QC: mCherry-GFP-FIS1[mt101-152]; MFN2: mitofusin 2; MMP: mitochondrial membrane potential; mROS: mitochondrial reactive oxygen species; MOI: multiplicity of infection; 2-NBDG: 2-(N-(7-nitrobenz-2-oxa-1, 3-diazol-4-yl) amino)-2-deoxyglucose; NDV: newcastle disease virus; OCR: oxygen consumption rate; siRNA: small interfering RNA; SIRT3: sirtuin 3; TCA: tricarboxylic acid; TCID: tissue culture infective doses.
Topics: AMP-Activated Protein Kinases; Animals; Autophagy; Energy Metabolism; Mitophagy; Newcastle disease virus; Reactive Oxygen Species; Sirtuin 3; Ubiquitin-Protein Ligases
PubMed: 34720029
DOI: 10.1080/15548627.2021.1990515 -
Frontiers in Molecular Biosciences 2023
PubMed: 38028532
DOI: 10.3389/fmolb.2023.1287885 -
Frontiers in Veterinary Science 2022Newcastle disease (ND) is an acute and highly contagious disease caused by the Newcastle disease virus (NDV) infecting poultry, which has caused great harm to the... (Review)
Review
Newcastle disease (ND) is an acute and highly contagious disease caused by the Newcastle disease virus (NDV) infecting poultry, which has caused great harm to the poultry industry around the world. Rapid diagnosis of NDV is important to early treatment and early institution of control measures. In this review, we comprehensively summarize the most recent research into NDV, including historical overview, molecular structure, and infection mechanism. We then focus on detection strategies for NDV, including virus isolation, serological assays (such as hemagglutination and hemagglutination-inhibition tests, enzyme linked immunosorbent assay, reporter virus neutralization test, Immunofluorescence assay, and Immune colloidal gold technique), molecular assays (such as reverse transcription polymerase chain reaction, real-time quantitative PCR, and loop-mediated isothermal amplification) and other assays. The performance of the different serological and molecular biology assays currently available was also analyzed. To conclude, we examine the limitations of currently available strategies for the detection of NDV to lay the groundwork for new detection assays.
PubMed: 35982920
DOI: 10.3389/fvets.2022.936251 -
Veterinary Research Nov 2022Newcastle disease (ND) is one of the most economically devastating infectious diseases affecting the poultry industry. Virulent Newcastle disease virus (NDV) can cause... (Review)
Review
Newcastle disease (ND) is one of the most economically devastating infectious diseases affecting the poultry industry. Virulent Newcastle disease virus (NDV) can cause high mortality and severe tissue lesions in the respiratory, gastrointestinal, neurological, reproductive and immune systems of poultry. Tremendous progress has been made in preventing morbidity and mortality caused by ND based on strict biosecurity and wide vaccine application. In recent decades, the continual evolution of NDV has resulted in a total of twenty genotypes, and genetic variation may be associated with disease outbreaks in vaccinated chickens. In some countries, the administration of genotype-matched novel vaccines in poultry successfully suppresses the circulation of virulent NDV strains in the field. However, virulent NDV is still endemic in many regions of the world, especially in low- and middle-income countries, impacting the livelihood of millions of people dependent on poultry for food. In ND-endemic countries, although vaccination is implemented for disease control, the lack of genotype-matched vaccines that can reduce virus infection and transmission as well as the inadequate administration of vaccines in the field undermines the effectiveness of vaccination. Dissection of the profiles of existing ND vaccines is fundamental for establishing proper vaccination regimes and developing next-generation vaccines. Therefore, in this article, we provide a broad review of commercial and experimental ND vaccines and promising new platforms for the development of next-generation vaccines.
Topics: Animals; Newcastle Disease; Chickens; Viral Vaccines; Newcastle disease virus; Poultry Diseases; Poultry
PubMed: 36435802
DOI: 10.1186/s13567-022-01118-w -
Current Opinion in Virology Oct 2023Newcastle disease virus (NDV) is an avian pathogen with an unsegmented negative-strand RNA genome. Properties such as the ease of genome modification, respiratory tract... (Review)
Review
Newcastle disease virus (NDV) is an avian pathogen with an unsegmented negative-strand RNA genome. Properties such as the ease of genome modification, respiratory tract tropism, and self-limiting replication in mammals make NDV an attractive vector for vaccine development. Experimental NDV-based vaccines against multiple human and animal pathogens elicited both systemic and mucosal immune responses and were protective in preclinical animal studies, but their real-life efficacy remains to be demonstrated. Only recently, the first results of clinical trials of NDV-based vaccines against SARS-CoV-2 became available, highlighting the challenges that need to be overcome to fully realize the potential of NDV as a platform for the rapid development of economically affordable and effective mucosal vaccines.
Topics: Animals; Humans; Newcastle disease virus; COVID-19 Vaccines; COVID-19; SARS-CoV-2; Mammals
PubMed: 37591130
DOI: 10.1016/j.coviro.2023.101348 -
Veterinary Medicine and Science Nov 2022Newcastle disease (ND) is an economically significant poultry disease worldwide. During field surveillance for ND in 2010 in Iran, a backyard chicken flock showed...
BACKGROUND
Newcastle disease (ND) is an economically significant poultry disease worldwide. During field surveillance for ND in 2010 in Iran, a backyard chicken flock showed clinical signs of ND with 100% mortality.
OBJECTIVES
We aimed to characterise genetically, biologically and epidemiologically an exotic virulent ND virus (NDV) detected in Iran.
METHODS
After observing high mortality, dead birds were sampled and then disposed of by burial, and the chicken house was disinfected. Tissue samples were molecularly tested for NDV. The genetic homogeneity of the isolate RT30/2010 was tested by plaque assay, and then a large virus plaque was used for the second step of plaque purification. Fusion and matrix complete genes were sequenced and used for genotyping and epidemiological tracing. We tested biological pathotypes using mean death time (MDT) and intracerebral pathogenicity index (ICPI) assays.
RESULTS
The isolate formed heterogeneous plaques in chicken embryo fibroblast cells. The second step of plaque purification produced homogeneous and large plaques. Phylogenetic analysis using both genes classified the virus into sub-genotype XIII.2.1. Nucleic acid and amino acid identities of RT30/2010 fusion gene with the closest available isolate SPVC/Karachi/NDV/43 are 97.95% and 98.73%, respectively. Isolate has RRRKRF motif at the fusion cleavage site, and pathogenicity tests showed MDT of 56.4 h and ICPI of 1.85.
CONCLUSIONS
This study presents the first detection and characterisation of a velogenic NDV of sub-genotype XIII.2.1 from Iran. Our follow-up surveillance for ND shows that timely virus detection and carcass management have led to the cessation of virus transmission in Iran.
Topics: Animals; Chick Embryo; Newcastle disease virus; Chickens; Phylogeny; Iran; Newcastle Disease; Genotype
PubMed: 36084260
DOI: 10.1002/vms3.928 -
Viruses May 2022The COVID-19 pandemic has highlighted the need for efficient vaccine platforms that can rapidly be developed and manufactured on a large scale to immunize the population... (Review)
Review
The COVID-19 pandemic has highlighted the need for efficient vaccine platforms that can rapidly be developed and manufactured on a large scale to immunize the population against emerging viruses. Viral-vectored vaccines are prominent vaccine platforms that have been approved for use against the Ebola virus and SARS-CoV-2. The Newcastle Disease Virus is a promising viral vector, as an avian paramyxovirus that infects poultry but is safe for use in humans and other animals. NDV has been extensively studied not only as an oncolytic virus but also a vector for human and veterinary vaccines, with currently ongoing clinical trials for use against SARS-CoV-2. However, there is a gap in NDV research when it comes to process development and scalable manufacturing, which are critical for future approved vaccines. In this review, we summarize the advantages of NDV as a viral vector, describe the steps and limitations to generating recombinant NDV constructs, review the advances in human and veterinary vaccine candidates in pre-clinical and clinical tests, and elaborate on production in embryonated chicken eggs and cell culture. Mainly, we discuss the existing data on NDV propagation from a process development perspective and provide prospects for the next steps necessary to potentially achieve large-scale NDV-vectored vaccine manufacturing.
Topics: Animals; COVID-19; Humans; Newcastle disease virus; Pandemics; SARS-CoV-2; Viral Vaccines
PubMed: 35632717
DOI: 10.3390/v14050975 -
Viruses Oct 2022Newcastle Disease Virus (NDV) genotype VII is a highly pathogenic that has caused multiple outbreaks among poultry in Egypt since 2011. This study aimed to observe the...
Newcastle Disease Virus (NDV) genotype VII is a highly pathogenic that has caused multiple outbreaks among poultry in Egypt since 2011. This study aimed to observe the prevalence and genetic diversity of NDV prevailing in domestic and wild birds in Egyptian governorates. A total of 37 oropharyngeal swabs from wild birds and 101 swabs from domestic bird flocks including chickens, ducks, turkeys, and pelicans, were collected from different geographic regions within 13 governorates during 2019-2020. Virus isolation and propagation via embryonated eggs revealed 91 swab samples produced allantoic fluid containing haemagglutination activity, suggestive of virus presence. The use of RT-PCR targeted to the F gene successfully detected NDV in 85 samples. The geographical prevalence of NDV was isolated in 12 governorates in domestic birds, migratory, and non-migratory wild birds. Following whole genome sequencing, we assembled six NDV genome sequences (70-99% of genome coverage), including five full F gene sequences. All NDV strains carried high virulence, with phylogenetic analysis revealing that the strains belonged to class II within genotype VII.1.1. The genetically similar yet geographically distinct virulent NDV isolates in poultry and a wild bird may allude to an external role contributing to the dissemination of NDV in poultry populations across Egypt. One such contribution may be the migratory behaviour of wild birds; however further investigation must be implemented to support the findings of this study. Additionally, continued genomic surveillance in both wild birds and poultry would be necessary for monitoring NDV dissemination and genetic diversification across Egypt, with the aim of controlling the disease and protecting poultry production.
Topics: Animals; Newcastle Disease; Poultry; Egypt; Phylogeny; Prevalence; Chickens; Newcastle disease virus; Animals, Wild; Genotype; Poultry Diseases; Animals, Domestic
PubMed: 36298799
DOI: 10.3390/v14102244 -
Journal of Virology Mar 2023Viruses require host cell metabolic reprogramming to satisfy their replication demands; however, the mechanism by which the Newcastle disease virus (NDV) remodels...
Viruses require host cell metabolic reprogramming to satisfy their replication demands; however, the mechanism by which the Newcastle disease virus (NDV) remodels nucleotide metabolism to support self-replication remains unknown. In this study, we demonstrate that NDV relies on the oxidative pentose phosphate pathway (oxPPP) and the folate-mediated one-carbon metabolic pathway to support replication. In concert with [1,2-C] glucose metabolic flow, NDV used oxPPP to promote pentose phosphate synthesis and to increase antioxidant NADPH production. Metabolic flux experiments using [2,3,3-H] serine revealed that NDV increased one-carbon (1C) unit synthesis flux through the mitochondrial 1C pathway. Interestingly, methylenetetrahydrofolate dehydrogenase (MTHFD2) was upregulated as a compensatory mechanism for insufficient serine availability. Unexpectedly, direct knockdown of enzymes in the one-carbon metabolic pathway, except for cytosolic MTHFD1, significantly inhibited NDV replication. Specific complementation rescue experiments on small interfering RNA (siRNA)-mediated knockdown further revealed that only a knockdown of MTHFD2 strongly restrained NDV replication and was rescued by formate and extracellular nucleotides. These findings indicated that NDV replication relies on MTHFD2 to maintain nucleotide availability. Notably, nuclear MTHFD2 expression was increased during NDV infection and could represent a pathway by which NDV steals nucleotides from the nucleus. Collectively, these data reveal that NDV replication is regulated by the c-Myc-mediated 1C metabolic pathway and that the mechanism of nucleotide synthesis for viral replication is regulated by MTHFD2. Newcastle disease virus (NDV) is a dominant vector for vaccine and gene therapy that accommodates foreign genes well but can only infect mammalian cells that have undergone cancerous transformation. Understanding the remodeling of nucleotide metabolic pathways in host cells by NDV proliferation provides a new perspective for the precise use of NDV as a vector or in antiviral research. In this study, we demonstrated that NDV replication is strictly dependent on pathways involved in redox homeostasis in the nucleotide synthesis pathway, including the oxPPP and the mitochondrial one-carbon pathway. Further investigation revealed the potential involvement of NDV replication-dependent nucleotide availability in promoting MTHFD2 nuclear localization. Our findings highlight the differential dependence of NDV on enzymes for one-carbon metabolism, and the unique mechanism of action of MTHFD2 in viral replication, thereby providing a novel target for antiviral or oncolytic virus therapy.
Topics: Animals; Methylenetetrahydrofolate Dehydrogenase (NADP); Newcastle Disease; Newcastle disease virus; Nucleotides; Serine; Virus Replication; Cell Line; A549 Cells; Humans; Mesocricetus; Gene Knockdown Techniques; Protein Transport; Mitochondria; Up-Regulation
PubMed: 36794935
DOI: 10.1128/jvi.00016-23