ABSTRACT
Newcastle disease virus (NDV), an avian paramyxovirus, causes major economic losses in the poultry industry worldwide. NDV strains are classified as avirulent, moderately virulent, or virulent according to the severity of the disease they cause. In order to gain a deeper understanding of the molecular mechanisms of virus-host interactions, we conducted Illumina HiSeq-based RNA-Seq analysis on chicken embryo fibroblast (DF1) cells during the first 24 hours of infection with NDV strain Komarov. Comparative analysis of uninfected DF1 cells versus NDV-infected DF1 cells at 6, 12, and 24 h postinfection identified 462, 459, and 410 differentially expressed genes, respectively. The findings revealed an increase in the expression of genes linked to the MAPK signalling pathway in the initial stages of NDV infection. This overexpression potentially aids viral multiplication while hindering pathogen detection and subsequent immune responses from the host. Our findings provide initial insights into the early responses of DF1 cells to NDV infection.
Subject(s)
Chickens , Fibroblasts , Gene Expression Profiling , Host-Pathogen Interactions , Newcastle Disease , Newcastle disease virus , Newcastle disease virus/genetics , Newcastle disease virus/pathogenicity , Newcastle disease virus/physiology , Animals , Newcastle Disease/virology , Newcastle Disease/immunology , Chickens/virology , Fibroblasts/virology , Host-Pathogen Interactions/genetics , Chick Embryo , Cell Line , Transcriptome , Poultry Diseases/virology , Poultry Diseases/genetics , Virus Replication/geneticsABSTRACT
Infectious bursal disease (IBD) is a widespread problem in the poultry industry, and vaccination is the primary preventive method. However, moderately virulent vaccines may damage the bursa, necessitating the development of a safe and effective vaccine. The Newcastle disease virus (NDV) has been explored as a vector for vaccine development. In this study, reverse genetic technology was used to obtain three recombinant viruses, namely, rClone30-VP2L (P/M)-chGM-CSF (NP), rClone30-chGM-CSF (P/M)-VP2L (NP), and rClone30-VP2L-chGM-CSF (P/M). Animal experiments showed that the three biological adjuvant bivalent vaccines effectively increased anti-NDV and anti-infectious bursal disease virus (IBDV) titres, enhancing both humoral and cellular immune responses in chickens without leading to any harm. Amongst the three biological adjuvant bivalent vaccines, the rClone30-chGM-CSF (P/M)-VP2L (NP) group had higher levels of anti-NDV antibodies at 14 days after the first immunization and stimulated a greater humoral immune response in 7-10 days. While, the rClone30-VP2L (P/M)-chGM-CSF (NP) group was the most effective in producing a higher level of IBDV antibody response. In conclusion, these three vaccines can induce immune responses more rapidly and effectively, streamline production processes, be cost-effective, and provide a new avenue for the development of Newcastle disease (ND) and IBD bivalent vaccines.
Subject(s)
Antibodies, Viral , Birnaviridae Infections , Chickens , Infectious bursal disease virus , Newcastle Disease , Newcastle disease virus , Poultry Diseases , Viral Vaccines , Animals , Viral Vaccines/immunology , Poultry Diseases/prevention & control , Poultry Diseases/virology , Poultry Diseases/immunology , Birnaviridae Infections/prevention & control , Birnaviridae Infections/immunology , Birnaviridae Infections/veterinary , Newcastle disease virus/immunology , Newcastle disease virus/genetics , Infectious bursal disease virus/immunology , Infectious bursal disease virus/genetics , Newcastle Disease/prevention & control , Newcastle Disease/immunology , Antibodies, Viral/blood , Immunity, Humoral , Adjuvants, Immunologic/administration & dosage , Adjuvants, Vaccine , Immunity, Cellular , VaccinationABSTRACT
BACKGROUND: Haemagglutinin-neuraminidase (HN) is one of the membrane proteins of Newcastle disease virus (NDV) that plays a significant role during host viral infection. Therefore, antibodies against HN are vital for the host's ability to protect itself against NDV infection due to their critical functions in viral infection. As a result, HN has been a candidate protein in vaccine development against the Newcastle disease virus. METHODS: This report used the full-length sequence of the HN protein of NDV isolated in Iran (VIId subgenotype). We characterize and identify amino acid substitutions in comparison to other more prevalent NDV genotypes, VII subgenotypes and vaccine strains. Furthermore, bioinformatics tools were applied to determine the three-dimensional structure, molecular dynamics simulation and prediction of B-cell antigenic epitopes. RESULTS: The results showed that the antigenic regions of our isolate are quite comparable to the other VII subgenotypes of NDV isolated from different geographical places. Moreover, by employing the final 3D structure of our HN protein, the amino acid residues are proposed as a B-cell epitope by epitope prediction servers, which leads to the introduction of linear and conformational antigenic sites. CONCLUSIONS: Immunoinformatic vaccine design principles currently exhibit tremendous potential for developing a new generation of candidate vaccines quickly and economically to eradicate infectious viruses, including the NDV. In order to accomplish this, focus is directed on residues that might be considered antigenic.
Subject(s)
Genotype , HN Protein , Newcastle disease virus , Newcastle disease virus/genetics , Newcastle disease virus/immunology , HN Protein/genetics , HN Protein/chemistry , Amino Acid Sequence , Animals , Iran , Base Sequence , Chickens , Poultry Diseases/virology , Newcastle Disease/virologyABSTRACT
Sialoglycan-binding enveloped viruses often possess receptor-destroying activity to avoid being immobilized by non-functional decoy receptors. Sialic acid (Sia)-binding paramyxoviruses contain a hemagglutinin-neuraminidase (HN) protein that possesses both Sia-binding and -cleavage activities. The multivalent, dynamic receptor interactions of paramyxovirus particles provide virion motility and are a key determinant of host tropism. However, such multivalent interactions have not been exhaustively analyzed, because such studies are complicated by the low affinity of the individual interactions and the requirement of high titer virus stocks. Moreover, the dynamics of multivalent particle-receptor interactions are difficult to predict from Michaelis-Menten enzyme kinetics. Therefore, we here developed Ni-NTA nanoparticles that multivalently display recombinant soluble HN tetramers via their His tags (HN-NPs). Applying this HN-NP platform to Newcastle disease virus (NDV), we investigated using biolayer interferometry (BLI) the role of important HN residues in receptor-interactions and analyzed long-range effects between the catalytic site and the second Sia binding site (2SBS). The HN-NP system was also applicable to other paramyxoviruses. Comparative analysis of HN-NPs revealed and confirmed differences in dynamic receptor-interactions between type 1 human and murine parainfluenza viruses as well as of lab-adapted and clinical isolates of human parainfluenza virus type 3, which are likely to contribute to differences in tropism of these viruses. We propose this novel platform to be applicable to elucidate the dynamics of multivalent-receptor interactions important for host tropism and pathogenesis, particularly for difficult to grow sialoglycan-binding (paramyxo)viruses.
Subject(s)
HN Protein , Nanoparticles , Newcastle disease virus , Receptors, Virus , HN Protein/metabolism , HN Protein/genetics , Animals , Newcastle disease virus/metabolism , Newcastle disease virus/physiology , Newcastle disease virus/genetics , Receptors, Virus/metabolism , Humans , N-Acetylneuraminic Acid/metabolismABSTRACT
Newcastle disease virus (NDV) is an avian pathogen with an unsegmented negative-strand RNA genome that belongs to the Paramyxoviridae family. While primarily pathogenic in birds, NDV presents no threat to human health, rendering it a safe candidate for various biomedical applications. Extensive research has highlighted the potential of NDV as a vector for vaccine development and gene therapy, owing to its transcriptional modularity, low recombination rate, and lack of a DNA phase during replication. Furthermore, NDV exhibits oncolytic capabilities, efficiently eliciting antitumor immune responses, thereby positioning it as a promising therapeutic agent for cancer treatment. This article comprehensively reviews the biological characteristics of NDV, elucidates the molecular mechanisms underlying its oncolytic properties, and discusses its applications in the fields of vaccine vector development and tumor therapy.
Subject(s)
Genetic Vectors , Neoplasms , Newcastle disease virus , Oncolytic Virotherapy , Oncolytic Viruses , Newcastle disease virus/genetics , Newcastle disease virus/immunology , Animals , Humans , Genetic Vectors/genetics , Neoplasms/therapy , Neoplasms/immunology , Oncolytic Virotherapy/methods , Oncolytic Viruses/genetics , Oncolytic Viruses/immunology , Genetic Therapy/methods , Viral Vaccines/immunology , Viral Vaccines/genetics , Newcastle Disease/prevention & control , Newcastle Disease/therapy , Newcastle Disease/virology , Newcastle Disease/immunology , Vaccine Development/methodsABSTRACT
The second-leading cause of death, cancer, poses a significant threat to human life. Innovations in cancer therapies are crucial due to limitations in traditional approaches. Newcastle disease virus (NDV), a nonpathogenic oncolytic virus, exhibits multifunctional anticancer properties by selectively infecting, replicating, and eliminating tumor cells. To enhance NDV's antitumor activity, four oncolytic NDV viruses were developed, incorporating IL24 and/or GM-CSF genes at different gene loci using reverse genetics. In vitro experiments revealed that oncolytic NDV virus augmented the antitumor efficacy of the parental virus rClone30, inhibiting tumor cell proliferation, inducing tumor cell fusion, and promoting apoptosis. Moreover, NDV carrying the IL24 gene inhibited microvessel formation in CAM experiments. Evaluation in a mouse model of liver cancer confirmed the therapeutic efficacy of oncolytic NDV viral therapy. Tumors in mice treated with oncolytic NDV virus significantly decreased in size, accompanied by tumor cell detachment and apoptosis evident in pathological sections. Furthermore, oncolytic NDV virus enhanced T cell and dendritic cell production and substantially improved the survival rate of mice with hepatocellular carcinoma, with rClone30-IL24(P/M) demonstrating significant therapeutic effects. This study establishes a basis for utilizing oncolytic NDV virus as an antitumor agent in clinical practice.
Subject(s)
Interleukins , Newcastle disease virus , Oncolytic Virotherapy , Oncolytic Viruses , Animals , Newcastle disease virus/genetics , Newcastle disease virus/physiology , Oncolytic Virotherapy/methods , Oncolytic Viruses/genetics , Oncolytic Viruses/physiology , Humans , Mice , Cell Line, Tumor , Interleukins/genetics , Interleukins/metabolism , Liver Neoplasms/therapy , Mice, Inbred BALB C , Carcinoma, Hepatocellular/therapy , Apoptosis , Neovascularization, Pathologic/therapy , Cell Proliferation , Granulocyte-Macrophage Colony-Stimulating Factor/genetics , Granulocyte-Macrophage Colony-Stimulating Factor/metabolism , Dendritic Cells/immunology , T-Lymphocytes/immunologyABSTRACT
BACKGROUND: In order to prevent the emergence and spread of future variants of concern of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), developing vaccines capable of stopping transmission is crucial. The SARS-CoV-2 vaccine NDV-HXP-S can be administered live intranasally (IN) and thus induce protective immunity in the upper respiratory tract. The vaccine is based on Newcastle disease virus (NDV) expressing a stabilised SARS-CoV-2 spike protein. NDV-HXP-S can be produced as influenza virus vaccine at low cost in embryonated chicken eggs. METHODS: The NDV-HXP-S vaccine was genetically engineered to match the Omicron variants of concern (VOC) BA.1 and BA.5 and tested as an IN two or three dose vaccination regimen in female mice. Furthermore, female mice intramuscularly (IM) vaccinated with mRNA-lipid nanoparticles (LNPs) were IN boosted with NDV-HXP-S. Systemic humoral immunity, memory T cell responses in the lungs and spleens as well as immunoglobulin A (IgA) responses in distinct mucosal tissues were characterised. FINDINGS: NDV-HXP-S Omicron variant vaccines elicited high mucosal IgA and serum IgG titers against respective SARS-CoV-2 VOC in female mice following IN administration and protected against challenge from matched variants. Additionally, antigen-specific memory B cells and local T cell responses in the lungs were induced. Host immunity against the NDV vector did not interfere with boosting. Intramuscular vaccination with mRNA-LNPs was enhanced by IN NDV-HXP-S boosting resulting in improvement of serum neutralization titers and induction of mucosal immunity. INTERPRETATION: We demonstrate that NDV-HXP-S Omicron variant vaccines utilised for primary immunizations or boosting efficiently elicit humoral and cellular immunity. The described induction of systemic and mucosal immunity has the potential to reduce infection and transmission. FUNDING: This work was partially funded by the NIAIDCenters of Excellence for Influenza Research and Response (CEIRR) and by the NIAID Collaborative Vaccine Innovation Centers and by institutional funding from the Icahn School of Medicine at Mount Sinai. See under Acknowledgements for details.
Subject(s)
Administration, Intranasal , Antibodies, Viral , COVID-19 Vaccines , COVID-19 , Immunity, Humoral , Immunity, Mucosal , Newcastle disease virus , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Animals , Female , SARS-CoV-2/immunology , SARS-CoV-2/genetics , Mice , COVID-19 Vaccines/immunology , COVID-19 Vaccines/administration & dosage , COVID-19/prevention & control , COVID-19/immunology , Antibodies, Viral/immunology , Antibodies, Viral/blood , Spike Glycoprotein, Coronavirus/immunology , Spike Glycoprotein, Coronavirus/genetics , Newcastle disease virus/immunology , Newcastle disease virus/genetics , Immunity, Cellular , Immunoglobulin A/immunology , Nanoparticles/administration & dosage , Nanoparticles/chemistry , Antibodies, Neutralizing/immunology , Vaccination/methods , Humans , LiposomesABSTRACT
The majority of pigeon paramyxovirus type 1 (PPMV-1) strains are generally non-pathogenic to chickens; however, they can induce severe illness and high mortality rates in pigeons, leading to substantial economic repercussions. The genomes of 11 PPMV-1 isolates from deceased pigeons on meat pigeon farms during passive monitoring from 2009 to 2012 were sequenced and analyzed using polymerase chain reaction and phylogenetic analysis. The complete genome lengths of 11 isolates were approximately 15,192 nucleotides, displaying a consistent gene order of 3'-NP-P-M-F-HN-L-5'. ALL isolates exhibited the characteristic motif of 112RRQKRF117 at the fusion protein cleavage site, which is characteristic of velogenic Newcastle disease virus. Moreover, multiple mutations have been identified within the functional domains of the F and HN proteins, encompassing the fusion peptide, heptad repeat region, transmembrane domains, and neutralizing epitopes. Phylogenetic analysis based on sequences of the F gene unveiled that all isolates clustered within genotype VI in class II. Further classification identified at least two distinct sub-genotypes, with seven isolates classified as sub-genotype VI.2.1.1.2.2, whereas the others were classified as sub-genotype VI.2.1.1.2.1. This study suggests that both sub-genotypes were implicated in severe disease manifestation among meat pigeons, with sub-genotype VI.2.1.1.2.2 displaying an increasing prevalence among Shanghai's meat pigeon population since 2011. These results emphasize the value of developing pigeon-specific vaccines and molecular diagnostic tools for monitoring and proactively managing potential PPMV-1 outbreaks.
Subject(s)
Columbidae , Genome, Viral , Newcastle Disease , Newcastle disease virus , Phylogeny , Animals , Columbidae/virology , China/epidemiology , Newcastle disease virus/genetics , Newcastle disease virus/isolation & purification , Newcastle disease virus/classification , Newcastle Disease/virology , Newcastle Disease/epidemiology , Genotype , Farms , Meat/virologyABSTRACT
Newcastle disease (ND) is endemic in Angola. Several outbreaks of ND occurred in small backyard flocks and village chickens with high mortality in the southern provinces of the country, Cunene, Namibe and Huíla, in 2016 and 2018. In those years, 15 virulent ND virus (NDV) strains were isolated and grouped within subgenotype 2 of genotype VII (subgenotype VII.2). We now present a study on the thermostability of the isolates, aiming at the selection of the most thermostable strains that, after being genetically modified to reduce their virulence, can be adapted to the production of vaccines less dependent on cold chain and more adequate to protect native chickens against ND. Heat-inactivation kinetics of haemagglutinin (Ha) activity and infectivity (I) of the isolates were determined by incubating aliquots of virus at 56 °C for different time intervals. The two isolates from Namibe province showed a decrease in infectivity of 2 log10 in ≤ 10 min, therefore belonging to the I-phenotype, but while the NB1 isolate from 2016 maintained the Ha activity up to 30 min and was classified as thermostable virus (I-Ha+), the Ha activity of the 2018 NB2 isolate decreased by 2 log2 in 30 min, being classified as a thermolabile virus (I-Ha-). Of the 13 NDV isolates from Huíla province, 10 isolates were classified as thermostable, eight with phenotype I+Ha+ and 2 with phenotype I-Ha+. The other three isolates from this province were classified as thermolabile viruses (I-Ha-).Contribution: This study will contribute to the control and/or eradication of Newcastle disease virus in Angola. The thermostable viral strains isolated from chickens in the country can be genetically manipulated by reverse genetic technology in order to reduce their virulence and use them as a vaccine in the remote areas of Angola.
Subject(s)
Chickens , Newcastle Disease , Newcastle disease virus , Poultry Diseases , Newcastle disease virus/pathogenicity , Newcastle disease virus/genetics , Newcastle disease virus/classification , Animals , Newcastle Disease/virology , Newcastle Disease/epidemiology , Angola/epidemiology , Virulence , Poultry Diseases/virology , Poultry Diseases/epidemiology , Hot TemperatureABSTRACT
Vectored RNA vaccines offer a variety of possibilities to engineer targeted vaccines. They are cost-effective and safe, but replication competent, activating the humoral as well as the cellular immune system.This chapter focuses on RNA vaccines derived from negative-strand RNA viruses from the order Mononegavirales with special attention to Newcastle disease virus-based vaccines and their generation. It shall provide an overview on the advantages and disadvantages of certain vector platforms as well as their scopes of application, including an additional section on experimental COVID-19 vaccines.
Subject(s)
Genetic Vectors , Newcastle disease virus , mRNA Vaccines , Animals , Humans , COVID-19/prevention & control , COVID-19/immunology , COVID-19/virology , Genetic Vectors/genetics , Newcastle disease virus/genetics , Newcastle disease virus/immunology , RNA Viruses/genetics , RNA Viruses/immunology , SARS-CoV-2/immunology , SARS-CoV-2/genetics , Viral Vaccines/immunology , Viral Vaccines/genetics , mRNA Vaccines/genetics , mRNA Vaccines/immunologyABSTRACT
Newcastle disease virus (NDV) is the pathogen of a zoonosis that is primarily transmitted by poultry and has severe infectivity and a high fatality rate. Many studies have focused on the role of the NDV fusion (F) protein in the cell-cell membrane fusion process. However, little attention has been given to the heptad repeat region, HR4, which is located in the NDV F2 subunit. Here, site-directed mutants were constructed to study the function of the NDV F protein HR4 region and identify the key amino acids in this region. Nine conserved amino acids were substituted with alanine or the corresponding amino acid of other aligned paramyxoviruses. The desired mutants were examined for changes in fusogenic activity through three kinds of membrane fusion assays and expression and proteolysis through IFA, FACS and WB. The results showed that when conserved amino acids (L81, Y84, L88, L91, L92, P94, L95 and I99) were replaced with alanine, the fusogenic activity of the F protein was abolished, possibly because of failed protein expression not only on the cell surface but also inside cells. These data indicated that the conserved amino acids above in NDV F HR4 are critical for normal protein synthesis and expression, possibly for the stability of the F protein monomer, formation of trimer and conformational changes.
Subject(s)
Mutagenesis, Site-Directed , Newcastle disease virus , Viral Fusion Proteins , Virus Internalization , Newcastle disease virus/genetics , Newcastle disease virus/metabolism , Viral Fusion Proteins/genetics , Viral Fusion Proteins/metabolism , Animals , Amino Acid Substitution , Cell Line , Mutation , Proteolysis , Membrane FusionABSTRACT
A Newcastle disease virus (NDV)-vectored vaccine expressing clade 2.3.4.4b H5 Hemagglutinin was developed and assessed for efficacy against H5N1 highly pathogenic avian influenza (HPAI) in specific pathogen-free (SPF) chickens, broilers, and domestic ducks. In SPF chickens, the live recombinant NDV-vectored vaccine, rK148/22-H5, achieved complete survival against HPAI and NDV challenges and significantly reduced viral shedding. Notably, the live rK148/22-H5 vaccine conferred good clinical protection in broilers despite the presence of maternally derived antibodies. Good clinical protection was observed in domestic ducks, with decreased viral shedding. It demonstrated complete survival and reduced cloacal viral shedding when used as an inactivated vaccine from SPF chickens. The rK148/22-H5 vaccine is potentially a viable and supportive option for biosecurity measure, effectively protecting in chickens against the deadly clade 2.3.4.4b H5 HPAI and NDV infections. Furthermore, it aligns with the strategy of Differentiating Infected from Vaccinated Animals (DIVA).
Subject(s)
Antibodies, Viral , Chickens , Ducks , Hemagglutinin Glycoproteins, Influenza Virus , Influenza A Virus, H5N1 Subtype , Influenza in Birds , Newcastle disease virus , Vaccines, Inactivated , Vaccines, Synthetic , Virus Shedding , Animals , Chickens/immunology , Influenza in Birds/prevention & control , Influenza in Birds/immunology , Newcastle disease virus/immunology , Newcastle disease virus/genetics , Influenza A Virus, H5N1 Subtype/immunology , Influenza A Virus, H5N1 Subtype/genetics , Influenza A Virus, H5N1 Subtype/pathogenicity , Ducks/virology , Ducks/immunology , Vaccines, Inactivated/immunology , Vaccines, Inactivated/administration & dosage , Vaccines, Synthetic/immunology , Vaccines, Synthetic/administration & dosage , Vaccines, Synthetic/genetics , Antibodies, Viral/immunology , Antibodies, Viral/blood , Hemagglutinin Glycoproteins, Influenza Virus/immunology , Hemagglutinin Glycoproteins, Influenza Virus/genetics , Influenza Vaccines/immunology , Influenza Vaccines/administration & dosage , Influenza Vaccines/genetics , Specific Pathogen-Free Organisms , Vaccines, Attenuated/immunology , Vaccines, Attenuated/administration & dosage , Vaccines, Attenuated/genetics , Poultry Diseases/prevention & control , Poultry Diseases/virology , Poultry Diseases/immunology , Newcastle Disease/prevention & control , Newcastle Disease/immunology , Viral Vaccines/immunology , Viral Vaccines/administration & dosage , Viral Vaccines/geneticsABSTRACT
The haemagglutinin-neuraminidase (HN) protein, a vital membrane glycoprotein, plays a pivotal role in the pathogenesis of Newcastle disease virus (NDV). Previously, we demonstrated that a mutation in the HN protein is essential for the enhanced virulence of JS/7/05/Ch, a velogenic variant NDV strain originating from the mesogenic vaccine strain Mukteswar. Here, we explored the effects of the HN protein during viral infection in vitro using three viruses: JS/7/05/Ch, Mukteswar, and an HN-replacement chimeric NDV, JS/MukHN. Through microscopic observation, CCK-8, and LDH release assays, we demonstrated that compared with Mukteswar and JS/MukHN, JS/7/05/Ch intensified the cellular damage and mortality attributed to the mutant HN protein. Furthermore, JS/7/05/Ch induced greater levels of apoptosis, as evidenced by the activation of caspase-3/8/9. Moreover, JS/7/05/Ch promoted autophagy, leading to increased autophagosome formation and autophagic flux. Subsequent pharmacological experiments revealed that inhibition of apoptosis and autophagy significantly impacted virus replication and cell viability in the JS/7/05/Ch-infected group, whereas less significant effects were observed in the other two infected groups. Notably, the mutant HN protein enhanced JS/7/05/Ch-induced apoptosis and autophagy by suppressing NF-κB activation, while it mitigated the effects of NF-κB on NDV infection. Overall, our study offers novel insights into the mechanisms underlying the increased virulence of NDV and serves as a reference for the development of vaccines.
Subject(s)
Apoptosis , HN Protein , NF-kappa B , Newcastle Disease , Newcastle disease virus , Newcastle disease virus/physiology , Newcastle disease virus/genetics , Newcastle disease virus/pathogenicity , Animals , HN Protein/genetics , HN Protein/metabolism , Newcastle Disease/virology , NF-kappa B/metabolism , Poultry Diseases/virology , Chickens , Chick EmbryoABSTRACT
The emergence of new virulent genotypes and the continued genetic drift of Newcastle disease virus (NDV) implies that distinct genotypes of NDV are simultaneously evolving in different geographic locations across the globe, including throughout Africa, where NDV is an important veterinary pathogen. Expanding the genomic diversity of NDV increases the possibility of diagnostic and vaccine failures. In this review, we systematically analyzed the genetic diversity of NDV genotypes in Africa using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Information published between 1999 and 2022 were used to obtain the genetic background of different genotypes of NDV and their geographic distributions in Africa. The following genotypes were reported in Africa: I, II, III, IV, V, VI, VII, VIII, XI, XIII, XIV, XVII, XVIII, XX, and XXI. A new putative genotype has been detected in the Democratic Republic of the Congo. However, of 54 African countries, only 26 countries regularly report information on NDV outbreaks, suggesting that this number may be vastly underestimated. With eight different genotypes, Nigeria is the country with the greatest genotypic diversity of NDV among African countries. Genotype VII is the most prevalent group of NDV in Africa, which was reported in 15 countries. A phylogeographic analysis of NDV sequences revealed transboundary transmission of the virus in Eastern Africa, Western and Central Africa, and in Southern Africa. A regional and continental collaboration is recommended for improved NDV risk management in Africa.
Subject(s)
Genetic Variation , Genotype , Newcastle Disease , Newcastle disease virus , Phylogeny , Newcastle disease virus/genetics , Newcastle disease virus/classification , Newcastle disease virus/isolation & purification , Newcastle Disease/virology , Newcastle Disease/epidemiology , Africa/epidemiology , Animals , Genome, Viral , Vaccination/veterinary , Chickens/virology , Viral Vaccines/genetics , Viral Vaccines/immunology , Poultry Diseases/virology , Poultry Diseases/epidemiology , PhylogeographyABSTRACT
The Newcastle disease virus (NDV) affects wild and domesticated bird species, including commercial poultry. Although the diversity of NDV in domestic chickens is well documented, limited information is available about Newcastle disease (ND) outbreaks in other bird species. We report an annotated sequence of NDV/Vulture/Borjuri/01/22, an avirulent strain of NDV reported from Borjuri, Northeast India, in Himalayan Griffon vulture. The complete genome is 15,186 bases long with a fusion protein (F) cleavage site 112GRQGR↓L117. The phylogenetic analysis based on the F protein gene and the whole genome sequence revealed that the isolate from the vulture belongs to genotype II, sharing significant homology with vaccine strain LaSota. The study highlights the possible spillover of the virus from domestic to wild species through the food chain.
Subject(s)
Genome, Viral , Newcastle Disease , Newcastle disease virus , Phylogeny , Newcastle disease virus/genetics , Newcastle disease virus/isolation & purification , Newcastle disease virus/classification , Animals , Newcastle Disease/virology , Newcastle Disease/transmission , Genome, Viral/genetics , India , Genotype , Whole Genome Sequencing , Viral Fusion Proteins/geneticsABSTRACT
The transcription and replication of the Newcastle disease virus (NDV) strictly rely on the viral ribonucleoprotein (RNP) complex, which is composed of viral NP, P, L and RNA. However, it is not known whether other viral non-RNP proteins participate in this process for viral self-regulation. In this study, we used a minigenome (MG) system to identify the regulatory role of the viral non-RNP proteins V, M, W, F and HN. Among them, V significantly reduced MG-encoded reporter activity compared with the other proteins and inhibited the synthesis of viral mRNA and cRNA. Further, V interacted with NP. A mutation in residue W195 of V diminished V-NP interaction and inhibited inclusion body (IB) formation in NP-P-L-cotransfected cells. Furthermore, a reverse-genetics system for the highly virulent strain F48E9 was established. The mutant rF48E9-VW195R increased viral replication and apparently enhanced IB formation. In vivo experiments demonstrated that rF48E9-VW195R decreased virulence and retarded time of death. Overall, the results indicate that the V-NP interaction of the W195 mutant V decreased, which regulated viral RNA synthesis, IB formation, viral replication and pathogenicity. This study provides insight into the self-regulation of non-RNP proteins in paramyxoviruses.
Subject(s)
Newcastle disease virus , Viral Proteins , Virus Replication , Newcastle disease virus/genetics , Newcastle disease virus/physiology , Newcastle disease virus/metabolism , Animals , Viral Proteins/metabolism , Viral Proteins/genetics , Nucleoproteins/metabolism , Nucleoproteins/genetics , Newcastle Disease/virology , Newcastle Disease/metabolism , Cell Line , Gene Expression Regulation, Viral , RNA, Viral/genetics , RNA, Viral/metabolism , Chickens , Virulence , Protein Binding , MutationABSTRACT
The application of recombinant herpesvirus of turkey, expressing the H9 hemagglutinin gene from low pathogenic avian influenza virus (LPAIV) H9N2 and the avian orthoavulavirus-1 (AOAV-1) (commonly known as Newcastle Disease virus (NDV)) fusion protein (F) as an rHVT-H9-F vaccine, is an alternative to currently used classical vaccines. This study investigated H9- and ND-specific humoral and mucosal responses, H9-specific cell-mediated immunity, and protection conferred by the rHVT-H9-F vaccine in specific pathogen-free (SPF) chickens. Vaccination elicited systemic NDV F- and AIV H9-specific antibody response but also local antibodies in eye wash fluid and oropharyngeal swabs. The ex vivo H9-specific stimulation of splenic and pulmonary T cells in the vaccinated group demonstrated the ability of vaccination to induce systemic and local cellular responses. The clinical protection against a challenge using a LPAIV H9N2 strain of the G1 lineage isolated in Morocco in 2016 was associated with a shorter duration of shedding along with reduced viral genome load in the upper respiratory tract and reduced cloacal shedding compared to unvaccinated controls.
Subject(s)
Antibodies, Viral , Chickens , Influenza A Virus, H9N2 Subtype , Influenza Vaccines , Influenza in Birds , Virus Shedding , Animals , Influenza A Virus, H9N2 Subtype/immunology , Influenza A Virus, H9N2 Subtype/genetics , Chickens/immunology , Influenza in Birds/prevention & control , Influenza in Birds/immunology , Influenza Vaccines/immunology , Influenza Vaccines/administration & dosage , Antibodies, Viral/immunology , Antibodies, Viral/blood , Virus Shedding/immunology , Specific Pathogen-Free Organisms , Newcastle disease virus/immunology , Newcastle disease virus/genetics , Poultry Diseases/prevention & control , Poultry Diseases/immunology , Poultry Diseases/virology , Immunity, Cellular , Herpesvirus 1, Meleagrid/immunology , Herpesvirus 1, Meleagrid/genetics , Vaccination/methods , Immunity, Humoral , Genetic Vectors/immunology , Immunogenicity, Vaccine , Vaccines, Synthetic/immunology , Vaccines, Synthetic/administration & dosage , Hemagglutinin Glycoproteins, Influenza Virus/immunology , Hemagglutinin Glycoproteins, Influenza Virus/geneticsABSTRACT
Background: The use of traditional medicine against viral diseases in animal production has been practiced worldwide. Herbal extracts possess organic substances that would improve chicken body performance. Aim: The current study was designed to evaluate the effect of either thyme or ginseng oil in regard to their immune-modulatory, antiviral, and growth promoter properties. Methods: Two hundred and forty-one-day-old broiler chicks were allocated into eight equal groups as the following: group 1; nonvaccinated and nontreated and group 2; Newcastle disease virus (NDV) vaccinated and nontreated. Birds of groups 3 and 4 were treated with thyme oil (200 mg/l of drinking water for 12 hours/day) without or with NDV vaccination. Birds of groups 5 and 6 were treated with ginseng oil (200 mg/l of drinking water for 12 hours/day) without or with NDV vaccination. Birds of groups 7 and 8 were treated with a combination of ginseng oil (100 mg/l of drinking water) and thyme oil (100 mg/l of drinking water) for 12 hours/day. On the 35th day of life, birds in all the experimental groups were given 0.1 ml of a virulent genotype VIId NDV strain suspension containing 106.3 EID50/ml intramuscularly. Results: Administration of ginseng and thyme oils each alone or simultaneously to birds either vaccinated or nonvaccinated elicited a significant improvement in body performance parameters. Administration of thyme and ginseng each alone or concurrently to vaccinated birds (Gp 4, 6, and 8) induced a higher hemagglutination inhibition (HI) titer of 6, 7.3, and 6.3 log2 at 21 days of age, 6.7, 7.6, and 7 log2, at 28 days of age and 7, 8, and 6.8 log2 at 35 days of age, respectively. Challenge with vNDV genotype VII led to an increase in the NDV-specific HI-Ab titers 10 days post challenge in all the experimental groups. In addition, thyme, ginseng oils, or a combination of them improved the protection from mortality in vaccinated birds; by 100%, 100%, and 90%, respectively, compared with 80% protection from mortality in vaccinated-only birds post-NDV challenge. Moreover, NDV-vaccinated birds treated either with thyme; ginseng or their combination showed negative detection of the virus in both tracheal and cloacal swabs and nonvaccinated groups that received oils showed improvement in vNDV shedding in tracheal and cloacal swabs. Conclusion: It could be concluded that the administration of thyme and ginseng essential oils to broilers can improve productive performance parameters, stimulate humoral immunity against, and protect from vNDV infection.
Subject(s)
Drinking Water , Newcastle Disease , Panax , Plant Oils , Thymol , Thymus Plant , Animals , Newcastle disease virus/genetics , Chickens , Antibodies, Viral , OilsABSTRACT
Newcastle disease (ND) is a tremendously contagious avian infection with extensive monetary ramifications for the chicken zone. To reduce the effect of ND on the Saudi rooster enterprise, our analysis emphasizes the necessity of genotype-particular vaccinations, elevated surveillance, public recognition campaigns, and stepped-forward biosecurity. Data show that one-of-a-kind bird species, outdoor flocks, and nearby differences in susceptibility are all vulnerable. The pathogenesis consists of tropism in the respiratory and gastrointestinal structures and some genotypes boom virulence. Laboratory diagnostics use reverse transcription-polymerase chain reaction, sequencing, and serotyping among different strategies. Vital records are supplied through immune responses and serological trying out. Vaccination campaigns, biosecurity protocols, and emergency preparedness are all covered in prevention and manipulation techniques. Notably, co-circulating genotypes and disparities in immunization regulations worry Saudi Arabia. The effect of ND in Saudi Arabia is tested in this paper, with precise attention paid to immunological reaction, pathogenesis, susceptibility elements, laboratory analysis, and preventative and manipulation measures. Saudi Arabia can shield its bird region and beef up its defences against Newcastle's ailment, enforcing those hints into its policies.
Subject(s)
Cattle Diseases , Newcastle Disease , Poultry Diseases , Cattle , Animals , Male , Poultry , Chickens , Saudi Arabia , Newcastle disease virus/genetics , Poultry Diseases/epidemiology , Newcastle Disease/epidemiologyABSTRACT
Background: Despite the strict preventive immunization used in Egypt, Newcastle disease remained a prospective risk to the commercial and backyard chicken industries. The severe economic losses caused by the Newcastle disease virus (NDV) highlight the importance of the trials for the improvement and development of vaccines and vaccination programs. Aim: In the present study, we evaluated the effectiveness of two vaccination schemes for protection against the velogenic NDV (vNDV) challenge. Methods: Four groups (A-D) of commercial broiler chickens were used. Two groups (G-A and G-B) were vaccinated with priming live HB1 GII simultaneously with inactivated GVII vaccines at 5 days of age, then boosted with live LaSota GII vaccine in group A and live recombinant NDV GVII vaccine in group B on day 16. Groups A to C were challenged with NDV/Chicken/Egypt/ALEX/ZU-NM99/2019 strain (106 Embryo infective dose 50/0.1 ml) at 28 days of age. Results: Two vaccination schemes achieved 93.3% clinical protection against NDV with body gain enhancement; whereas, 80% of the unvaccinated-challenged birds died. On day 28, the mean HI antibody titers were 4.3 ± 0.33 and 5.3 ± 0.33 log2 in groups A and B, respectively. As well as both programs remarkably reduced virus shedding. The two vaccination schemes displayed close protection efficacy against the vNDV challenge. Conclusion: Therefore, using the combination of a live attenuated vaccine with an inactivated genetically matched strain vaccine and then boosting it with one of the available live vaccines could be considered one of the most effective programs against current field vNDV infection in Egypt.