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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 -
Vaccine Jul 2023Coronavirus disease 2019 (Covid-19) caused by the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) became a pandemic, causing significant burden on public...
Coronavirus disease 2019 (Covid-19) caused by the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) became a pandemic, causing significant burden on public health worldwide. Although the timely development and production of mRNA and adenoviral vector vaccines against SARS-CoV-2 have been successful, issues still exist in vaccine platforms for wide use and production. With the potential for proliferative capability and heat stability, the Newcastle disease virus (NDV)-vectored vaccine is a highly economical and conceivable candidate for treating emerging diseases. In this study, a recombinant NDV-vectored vaccine expressing the spike (S) protein of SARS-CoV-2, rK148/beta-S, was developed and evaluated for its efficacy against SARS-CoV-2 in K18-hACE-2 transgenic mice. Intramuscular vaccination with low dose (10 EID) conferred a survival rate of 76 % after lethal challenge of a SARS-CoV-2 beta (B.1.351) variant. When administered with a high dose (10 EID), vaccinated mice exhibited 100 % survival rate and reduced lung viral load against both beta and delta variants (B.1.617.2). Together with the protective immunity, rK148/beta-S is an accessible and cost-effective SARS-CoV-2 vaccine.
Topics: Mice; Animals; Humans; COVID-19; SARS-CoV-2; Spike Glycoprotein, Coronavirus; COVID-19 Vaccines; Newcastle disease virus; Mice, Transgenic; Viral Vaccines; Antibodies, Viral; Antibodies, Neutralizing
PubMed: 37355454
DOI: 10.1016/j.vaccine.2023.05.071 -
Journal of Veterinary Science Jan 2024The Newcastle disease virus (NDV) outbreak was first reported in Java Island, Indonesia, in 1926, which was then reported further in Newcastle-upon-Tyne, England.... (Review)
Review
The Newcastle disease virus (NDV) outbreak was first reported in Java Island, Indonesia, in 1926, which was then reported further in Newcastle-upon-Tyne, England. Nevertheless, the NDV is still endemic in Indonesia, with outbreaks occurring in free-range and commercial chicken farms. The dynamic evolution of the NDV has led to the further development of vaccines and diagnostic tools for more effective control of this virus. This paper discusses the history of the NDV occurrence, vaccines, the development of diagnostic tools, and the epidemiological condition of the NDV in Indonesia. Indonesia, which has the largest poultry population in the world after China, has challenges in preventing and controlling this virus that causes economic losses to the farmers and has an impact on the welfare of the poultry farming community in Indonesia.
Topics: Animals; Newcastle disease virus; Newcastle Disease; Indonesia; Viral Vaccines; Chickens; Poultry Diseases
PubMed: 38311318
DOI: 10.4142/jvs.23022 -
Emerging Microbes & Infections Dec 2023Pigeon paramyxovirus 1 (PPMV-1) is an antigenic host variant of avian paramyxovirus 1. Sporadic outbreaks of PPMV-1 infection have occurred in pigeons in China; however,...
Pigeon paramyxovirus 1 (PPMV-1) is an antigenic host variant of avian paramyxovirus 1. Sporadic outbreaks of PPMV-1 infection have occurred in pigeons in China; however, few cases of human PPMV-1 infection have been reported. The purpose of this article is to report a case of severe human PPMV-1 infection in an individual with probable post-COVID-19 syndrome (long COVID) who presented with rapidly progressing pulmonary infection. The patient was a 66-year-old man who was admitted to the intensive care unit 11 days after onset of pneumonia and recovered 64 days after onset. PPMV-1 was isolated from the patient's sputum and in cloacal smear samples from domesticated pigeons belonging to the patient's neighbour. Residual severe acute respiratory syndrome coronavirus 2 was detected in respiratory and anal swab samples from the patient. Sequencing analyses revealed that the PPMV-1 genome belonged to genotype VI.2.1.1.2.2 and had the 112RRQKRF117 motif in the cleavage site of the fusion protein, which is indicative of high virulence. This case of cross-species transmission of PPMV-1 from a pigeon to a human highlights the risk of severe PPMV-1 infection in immunocompromised patients, especially those with long COVID. Enhanced surveillance for increased risk of severe viral infection is warranted in this population.
Topics: Male; Animals; Humans; Aged; COVID-19; Columbidae; Newcastle disease virus; Post-Acute COVID-19 Syndrome; Antigenic Variation
PubMed: 37606967
DOI: 10.1080/22221751.2023.2251600 -
Virulence Dec 2023We previously demonstrated that two methyltransferase motifs, K-D-K-E and G-G-D, affect the pathogenicity of Newcastle disease virus (NDV) by regulating mRNA translation...
We previously demonstrated that two methyltransferase motifs, K-D-K-E and G-G-D, affect the pathogenicity of Newcastle disease virus (NDV) by regulating mRNA translation and virus transmission. Here, we compared the infectious centre area produced by the NDV strain, rSG10, and methyltransferase motifs mutant rSG10 strains in DF-1 cells. The results show that intercellular transmission was attenuated by methyltransferase motif mutations. We further determined the ability of mutant viruses to spread in cell-free and cell-to-cell situations. Cell-free transmission of rSG10-K1756A was not reduced, indicating that cell-to-cell transmission of rSG10-K1756A was decreased. Using a donor and target system, we demonstrated that NDV can spread from cell-to-cell directly. Furthermore, by comparing the protein distribution area of three strains when treated with 2% agar overlay, we found that rSG10-K1756A was defective in cell-to-cell transmission. Tunnelling nanotubes (TNTs) are an important mode for cell-to-cell transmission. Treatment of cells with cytochalasin D (CytoD) or nocodazole to inhibit the formation of TNTs, reduced protein levels in all strains, but rSG10-K1756A was the least affected. These results indicate that mutation of the K-D-K-E motif is likely to restricted the spread of NDV via TNTs. Finally, we observed that matrix protein (M) and fusion protein (F) promoted the formation of cellular extensions, which may be involved in the cell-to-cell spread of NDV. Our research reveals a novel mechanism by which methyltransferase motifs affect the cell-to-cell spread of NDV and provides insight into dissemination of paramyxoviruses.
Topics: Animals; Newcastle disease virus; Chickens; Mutation
PubMed: 36919461
DOI: 10.1080/21505594.2023.2186336 -
Scientific Reports Oct 2023Combining viruses and nanoparticles may be a way to successfully treat cancer and minimize adverse effects. The current work aimed to evaluate the efficacy of a specific...
Combining viruses and nanoparticles may be a way to successfully treat cancer and minimize adverse effects. The current work aimed to evaluate the efficacy of a specific combination of gold nanoparticles (GNPs) and Newcastle disease virus (NDV) to enhance the antitumor effect of breast cancer in both in vitro and in vivo models. Two human breast cancer cell lines (MCF-7 and AMJ-13) and a normal epithelial cell line (HBL-100) were used and treated with NDV and/or GNPs. The MTT assay was used to study the anticancer potentials of NDV and GNP. The colony formation assay and apoptosis markers were used to confirm the killing mechanisms of NDV and GNP against breast cancer cell lines. p53 and caspase-9 expression tested by the qRT-PCR technique. Our results showed that combination therapy had a significant killing effect against breast cancer cells. The findings demonstrated that NDV and GNPs induced apoptosis in cancer cells by activating caspase-9, the p53 protein, and other proteins related to apoptosis, which holds promise as a combination therapy for breast cancer.
Topics: Animals; Humans; Female; Oncolytic Virotherapy; Oncolytic Viruses; Caspase 9; Gold; Tumor Suppressor Protein p53; Cell Line, Tumor; Breast Neoplasms; Metal Nanoparticles; Apoptosis; Immunotherapy; Newcastle disease virus
PubMed: 37803068
DOI: 10.1038/s41598-023-42299-4 -
Virulence Dec 2024Newcastle disease virus (NDV) typically induces severe illness in poultry and results in significant economic losses for the worldwide poultry sector. NDV, an RNA virus...
Newcastle disease virus (NDV) typically induces severe illness in poultry and results in significant economic losses for the worldwide poultry sector. NDV, an RNA virus with a single-stranded negative-sense genome, is susceptible to mutation and immune evasion during viral transmission, thus imposing enormous challenges to avian health and poultry production. NDV is composed of six structural proteins and two nonstructural proteins that exert pivotal roles in viral infection and antiviral responses by interacting with host proteins. Nowadays, there is a particular focus on the mechanisms of virus-host protein interactions in NDV research, yet a comprehensive overview of such research is still lacking. Herein, we briefly summarize the mechanisms regarding the effects of virus-host protein interaction on viral infection, pathogenesis, and host immune responses. This review can not only enhance the present comprehension of the mechanism underlying NDV and host interplay, but also furnish a point of reference for the advancement of antiviral measures.
Topics: Animals; Antiviral Agents; Host Microbial Interactions; Immune Evasion; Newcastle disease virus; Virus Diseases
PubMed: 38193514
DOI: 10.1080/21505594.2023.2299182 -
PLoS Pathogens Feb 2024Lysosomes are acidic organelles that mediate the degradation and recycling of cellular waste materials. Damage to lysosomes can cause lysosomal membrane permeabilization...
Lysosomes are acidic organelles that mediate the degradation and recycling of cellular waste materials. Damage to lysosomes can cause lysosomal membrane permeabilization (LMP) and trigger different types of cell death, including apoptosis. Newcastle disease virus (NDV) can naturally infect most birds. Additionally, it serves as a promising oncolytic virus known for its effective infection of tumor cells and induction of intensive apoptotic responses. However, the involvement of lysosomes in NDV-induced apoptosis remains poorly understood. Here, we demonstrate that NDV infection profoundly triggers LMP, leading to the translocation of cathepsin B and D and subsequent mitochondria-dependent apoptosis in various tumor and avian cells. Notably, the released cathepsin B and D exacerbate NDV-induced LMP by inducing the generation of reactive oxygen species. Additionally, we uncover that the viral Hemagglutinin neuraminidase (HN) protein induces the deglycosylation and degradation of lysosome-associated membrane protein 1 (LAMP1) and LAMP2 dependent on its sialidase activity, which finally contributes to NDV-induced LMP and cellular apoptosis. Overall, our findings elucidate the role of LMP in NDV-induced cell apoptosis and provide novel insights into the function of HN during NDV-induced LMP, which provide innovative approaches for the development of NDV-based oncolytic agents.
Topics: Animals; Newcastle disease virus; HN Protein; Cathepsin B; Apoptosis; Lysosomes
PubMed: 38354122
DOI: 10.1371/journal.ppat.1011981 -
BMC Veterinary Research Oct 2023Thirty-two-day-old broiler chickens at a farm located in northwestern South Korea displayed adverse neurological symptoms including limping, lying down, and head...
BACKGROUND
Thirty-two-day-old broiler chickens at a farm located in northwestern South Korea displayed adverse neurological symptoms including limping, lying down, and head shaking. Approximately 2.1% of chickens died or were culled due to severe symptoms. Five carcasses were submitted to the Avian Disease Division of the Animal and Plant Quarantine Agency (APQA) for disease diagnosis.
RESULTS
Broilers displayed severe pericarditis and perihepatitis associated with gross lesions. Broilers also displayed microscopic lesions in the cerebrum and in the granular layer of the cerebellum, which were associated with multifocal perivascular cuffing and purulent necrosis in the cerebrum, and severe meningitis with heterophil and lymphocyte infiltration. Staphylococcus spp. were identified in the liver and heart using bacteriological culture. PCR/RT-PCR assays revealed that broilers were negative for avian Clostridium botulinum, Newcastle disease virus, and avian encephalomyelitis virus. Bacterial and viral metagenomic analysis of brain sample further revealed the presence of Pseudomonas spp. and Marek's disease virus, which are known etiological agents of chicken meningoencephalitis.
CONCLUSIONS
This study reports a diagnostic analysis of gross and histopathological lesions from 32-day-old broilers displaying unique neurological symptoms that revealed the presence of the several neurological diseases including meningoencephalitis. The causative agents associated with meningoencephalitis of broilers that had not been identified by routine diagnostic methods could be diagnosed by metagenomics, which proves the usefulness of metagenomics as a diagnostic tool for unknown neurological diseases in broilers.
Topics: Animals; Chickens; Newcastle disease virus; Newcastle Disease; Brain; Meningoencephalitis; Poultry Diseases
PubMed: 37798783
DOI: 10.1186/s12917-023-03732-y