-
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 Veterinary Science 2021Uganda is a Newcastle disease (ND) endemic country where the disease is controlled by vaccination using live LaSota (genotype II) and I (genotype I) vaccine strains....
Uganda is a Newcastle disease (ND) endemic country where the disease is controlled by vaccination using live LaSota (genotype II) and I (genotype I) vaccine strains. Resurgent outbreak episodes call for an urgent need to understand the antigenic diversity of circulating wild (AAvV1) strains. High mutation rates and the continuous emergence of genetic and antigenic variants that evade immunity make non-segmented RNA viruses difficult to control. Antigenic and functional analysis of the key viral surface proteins is a crucial step in understanding the antigen diversity between vaccine lineages and the endemic wild ND viruses in Uganda and designing ND peptide vaccines. In this study, we used computational analysis, phylogenetic characterization, and structural modeling to detect evolutionary forces affecting the predicted immune-dominant fusion (F) and hemagglutinin-neuraminidase (HN) proteins of isolates from waterfowl and poultry in Uganda compared with that in LaSota vaccine strain. Our findings indicate that mutational amino acid variations at the F protein in LaSota strain, 25 poultry wild-type and 30 waterfowl wild-type isolates were distributed at regions including the functional domains of B-cell epitopes or -glycosylation sites, cleavage site, fusion site that account for strain variations. Similarly, conserved regions of HN protein in 25 Ugandan domestic fowl isolates and the representative vaccine strain varied at the flanking regions and potential linear B-cell epitope. The fusion sites, signal peptides, cleavage sites, transmembrane domains, potential B-cell epitopes, and other specific regions of the two protein types in vaccine and wild viruses varied considerably at structure by effective online epitope prediction programs. Cleavage site of the waterfowl isolates had a typical avirulent motif of GGRQGR'L with the exception of one isolate which showed a virulent motif of GGRQKR'F. All the poultry isolates showed the GRRQKR'F motif corresponding to virulent strains. Amino acid sequence variations in both HN and F proteins of isolates from poultry, waterfowl, and vaccine strain were distributed over the length of the proteins with no detectable pattern, but using the experimentally derived 3D structure data revealed key-mapped mutations on the surfaces of the predicted conformational epitopes encompassing the experimental major neutralizing epitopes. The phylogenic tree constructed using the full F gene and partial F gene sequences of the isolates from poultry and waterfowl respectively, showed that Ugandan ND aquatic bird and poultry isolates share some functional amino acids in F sequences yet do remain unique at structure and the B-cell epitopes. Recombination analyses showed that the C-terminus and the rest of the F gene in poultry isolates originated from prevalent velogenic strains. Altogether, these could provide rationale for antigenic diversity in wild ND isolates of Uganda compared with the current ND vaccine strains.
PubMed: 34212016
DOI: 10.3389/fvets.2021.610375 -
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 -
Virology Journal Nov 2023Avian influenza (AI) is a disease caused by the avian influenza virus (AIV). These viruses spread naturally among wild aquatic birds worldwide and infect domestic...
BACKGROUND
Avian influenza (AI) is a disease caused by the avian influenza virus (AIV). These viruses spread naturally among wild aquatic birds worldwide and infect domestic poultry, other birds, and other animal species. Currently, real-time reverse transcription polymerase chain reaction (rRT-PCR) is mainly used to detect the presence of pathogens and has good sensitivity and specificity. However, the diagnosis requires sophisticated instruments under laboratory conditions, which significantly limits point-of-care testing (POCT). Rapid, reliable, non-lab-equipment-reliant, sensitive, and specific diagnostic tests are urgently needed for rapid clinical detection and diagnosis. Our study aimed to develop a reverse transcription recombinase polymerase amplification (RT-RPA)/CRISPR method which improves on these limitations.
METHODS
The Cas12a protein was purified by affinity chromatography with Ni-agarose resin and observed using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Specific CRISPR RNA (crRNA) and primers targeting the M and NP genes of the AIV were designed and screened. By combining RT-RPA with the Cas12a/crRNA trans-cleavage system, a detection system that uses fluorescence readouts under blue light or lateral flow strips was established. Sensitivity assays were performed using a tenfold dilution series of plasmids and RNA of the M and NP genes as templates. The specificity of this method was determined using H1-H16 subtype AIVs and other avian pathogens, such as newcastle disease virus (NDV), infectious bursal disease virus (IBDV), and infectious bronchitis virus (IBV).
RESULTS
The results showed that the method was able to detect AIV and that the detection limit can reach 6.7 copies/μL and 12 copies/μL for the M and NP gene, respectively. In addition, this assay showed no cross-reactivity with other avian-derived RNA viruses such as NDV, IBDV, and IBV. Moreover, the detection system presented 97.5% consistency and agreement with rRT-PCR and virus isolation for detecting samples from poultry. This portable and accurate method has great potential for AIV detection in the field.
CONCLUSION
An RT-RPA/CRISPR method was developed for rapid, sensitive detection of AIV. The new system presents a good potential as an accurate, user-friendly, and inexpensive platform for point-of-care testing applications.
Topics: Animals; Influenza in Birds; CRISPR-Cas Systems; Influenza A virus; Birds; Poultry; Sensitivity and Specificity; Real-Time Polymerase Chain Reaction; Newcastle disease virus; RNA
PubMed: 37957729
DOI: 10.1186/s12985-023-02232-7 -
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 -
Journal of Virology Mar 2022REC8 meiotic recombination protein (REC8) is a member of structural maintenance of chromosome (SMC) protein partners, which play an important role in meiosis, antitumor...
REC8 meiotic recombination protein (REC8) is a member of structural maintenance of chromosome (SMC) protein partners, which play an important role in meiosis, antitumor activity, and sperm formation. As the adaptor proteins of RIG-I-like receptor (RLR) signaling and cyclic GMP-AMP synthase (cGAS)-DNA signaling, the activity and stability of MAVS (mitochondrial antiviral signaling protein; also known as VISA, Cardif, and IPS-1) and STING (stimulator of interferon genes; also known as MITA) are critical for innate immunity. Here, we report that REC8 interacts with MAVS and STING and inhibits their ubiquitination and subsequent degradation, thereby promoting innate antiviral signaling. REC8 is upregulated through the JAK-STAT signaling pathway during viral infection. Knockdown of REC8 impairs the innate immune responses against vesicular stomatitis virus (VSV), Newcastle disease virus (NDV), and herpes simplex virus (HSV). Mechanistically, during infection with viruses, the SUMOylated REC8 is transferred from the nucleus to the cytoplasm and then interacts with MAVS and STING to inhibit their K48-linked ubiquitination triggered by RNF5. Moreover, REC8 promotes the recruitment of TBK1 to MAVS and STING. Thus, REC8 functions as a positive modulator of innate immunity. Our work highlights a previously undocumented role of meiosis-associated protein REC8 in regulating innate immunity. The innate immune response is crucial for the host to resist the invasion of viruses and other pathogens. STING and MAVS play a critical role in the innate immune response to DNA and RNA viral infection, respectively. In this study, REC8 promoted the innate immune response by targeting STING and MAVS. Notably, REC8 interacts with MAVS and STING in the cytoplasm and inhibits K48-linked ubiquitination of MAVS and STING triggered by RNF5, stabilizing MAVS and STING protein to promote innate immunity and gradually inhibiting viral infection. Our study provides a new insight for the study of antiviral innate immunity.
Topics: Adaptor Proteins, Signal Transducing; Animals; Antiviral Agents; Cell Cycle Proteins; Immunity, Innate; Membrane Proteins; Newcastle disease virus; Simplexvirus; Ubiquitination; Vesicular stomatitis Indiana virus; Virus Diseases
PubMed: 35107381
DOI: 10.1128/jvi.02175-21 -
Discovery Medicine 2020Newcastle disease virus (NDV) replicates in the cytoplasm and disintegrates the host genome or participates in recombination, and has a strong affinity for tumor cells.... (Review)
Review
Newcastle disease virus (NDV) replicates in the cytoplasm and disintegrates the host genome or participates in recombination, and has a strong affinity for tumor cells. These characteristics make it safer and more attractive than retroviruses or certain other DNA viruses, and one of the most potential oncolytic viruses used in oncolytic therapy. The construction of recombinant NDV (rNDV) using reverse genetics technology with NDV as a gene delivery vector has also enabled NDV in gene therapy approaches for treating cancer and other diseases. rNDV can not only stably express exogenous therapeutic genes, but also enhance the ability of the virus to kill tumor cells and induce host anti-tumor immune response. This article reviews the molecular characteristics, anti-tumor mechanisms, and the applications of NDV in cancer therapy.
Topics: Animals; Cancer Vaccines; Cell Line, Tumor; Disease Models, Animal; Genetic Therapy; Genetic Vectors; Humans; Neoplasms; Newcastle disease virus; Oncolytic Virotherapy; Oncolytic Viruses; Virus Replication
PubMed: 33357361
DOI: No ID Found -
International Journal of Medical... 2021This article reviews the preclinical research, clinical application and development of Newcastle disease virus (NDV) in the field of cancer therapy. Based on the... (Review)
Review
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.
Topics: Animals; Cancer Vaccines; Cell Line, Tumor; Combined Modality Therapy; Dendritic Cells; Disease Models, Animal; Drug Resistance, Neoplasm; Genetic Engineering; Humans; Immune Checkpoint Inhibitors; Immune Checkpoint Proteins; Immunotherapy; Killer Cells, Natural; Macrophages; Monocytes; Neoplasms; Newcastle disease virus; Oncolytic Virotherapy; Tumor Escape; Tumor Microenvironment; Up-Regulation; Vaccines, Attenuated; Vaccines, Synthetic; Viral Vaccines
PubMed: 33967605
DOI: 10.7150/ijms.59185