Newcastle disease virus activates diverse signaling pathways via Src to facilitate virus entry into host macrophages.

As an intrinsic cellular mechanism responsible for the internalization of extracellular ligands and membrane components, caveolae-mediated endocytosis (CavME) is also exploited by certain pathogens for endocytic entry [e.g., Newcastle disease virus (NDV) of paramyxovirus]. However, the molecular mechanisms of NDV-induced CavME remain poorly understood. Herein, we demonstrate that sialic acid-containing gangliosides, rather than glycoproteins, were utilized by NDV as receptors to initiate the endocytic entry of NDV into HD11 cells. The binding of NDV to gangliosides induced the activation of a non-receptor tyrosine kinase, Src, leading to the phosphorylation of caveolin-1 (Cav1) and dynamin-2 (Dyn2), which contributed to the endocytic entry of NDV. Moreover, an inoculation of cells with NDV-induced actin cytoskeletal rearrangement through Src to facilitate NDV entry via endocytosis and direct fusion with the plasma membrane. Subsequently, unique members of the Rho GTPases family, RhoA and Cdc42, were activated by NDV in a Src-dependent manner. Further analyses revealed that RhoA and Cdc42 regulated the activities of specific effectors, cofilin and myosin regulatory light chain 2, responsible for actin cytoskeleton rearrangement, through diverse intracellular signaling cascades. Taken together, our results suggest that an inoculation of NDV-induced Src-mediated cellular activation by binding to ganglioside receptors. This process orchestrated NDV endocytic entry by modulating the activities of caveolae-associated Cav1 and Dyn2, as well as specific Rho GTPases and downstream effectors. IMPORTANCE: In general, it is known that the paramyxovirus gains access to host cells through direct penetration at the plasma membrane; however, emerging evidence suggests more complex entry mechanisms for paramyxoviruses. The endocytic entry of Newcastle disease virus (NDV), a representative member of the paramyxovirus family, into multiple types of cells has been recently reported. Herein, we demonstrate the binding of NDV to induce ganglioside-activated Src signaling, which is responsible for the endocytic entry of NDV through caveolae-mediated endocytosis. This process involved Src-dependent activation of the caveolae-associated Cav1 and Dyn2, as well as specific Rho GTPase and downstream effectors, thereby orchestrating the endocytic entry process of NDV. Our findings uncover a novel molecular mechanism of endocytic entry of NDV into host cells and provide novel insight into paramyxovirus mechanisms of entry.

The Ca2+-dependent phosphatase calcineurin dephosphorylates TBK1 to suppress antiviral innate immunity.

Tumor necrosis factor receptor-associated factor family member-associated NF-κB activator-binding kinase 1 (TBK1) plays a key role in the induction of the type 1 interferon (IFN-I) response, which is an important component of innate antiviral defense. Viruses target calcium (Ca2+) signaling networks, which participate in the regulation of the viral life cycle, as well as mediate the host antiviral response. Although many studies have focused on the role of Ca2+ signaling in the regulation of IFN-I, the relationship between Ca2+ and TBK1 in different infection models requires further elucidation. Here, we examined the effects of the Newcastle disease virus (NDV)-induced increase in intracellular Ca2+ levels on the suppression of host antiviral responses. We demonstrated that intracellular Ca2+ increased significantly during NDV infection, leading to impaired IFN-I production and antiviral immunity through the activation of calcineurin (CaN). Depletion of Ca²+ was found to lead to a significant increase in virus-induced IFN-I production resulting in the inhibition of viral replication. Mechanistically, the accumulation of Ca2+ in response to viral infection increases the phosphatase activity of CaN, which in turn dephosphorylates and inactivates TBK1 in a Ca2+-dependent manner. Furthermore, the inhibition of CaN on viral replication was counteracted in TBK1 knockout cells. Together, our data demonstrate that NDV hijacks Ca2+ signaling networks to negatively regulate innate immunity via the CaN-TBK1 signaling axis. Thus, our findings not only identify the mechanism by which viruses exploit Ca2+ signaling to evade the host antiviral response but also, more importantly, highlight the potential role of Ca2+ homeostasis in the viral innate immune response.IMPORTANCEViral infections disrupt intracellular Ca2+ homeostasis, which affects the regulation of various host processes to create conditions that are conducive for their own proliferation, including the host immune response. The mechanism by which viruses trigger TBK1 activation and IFN-I induction through viral pathogen-associated molecular patterns has been well defined. However, the effects of virus-mediated Ca2+ imbalance on the IFN-I pathway requires further elucidation, especially with respect to TBK1 activation. Herein, we report that NDV infection causes an increase in intracellular free Ca2+ that leads to activation of the serine/threonine phosphatase CaN, which subsequently dephosphorylates TBK1 and negatively regulates IFN-I production. Furthermore, depletion of Ca2+ or inhibition of CaN activity exerts antiviral effects by promoting the production of IFN-I and inhibiting viral replication. Thus, our results reveal the potential role of Ca2+ in the innate immune response to viruses and provide a theoretical reference for the treatment of viral infectious diseases.

Cytokine expression, protection and shedding reduction induced by the combination of lipopolysaccharide with Montanoid ISA71 in oil-based Newcastle disease vaccine.

Oil-based inactivated ND vaccines are a commonly used control strategy for this endemic disease in Egypt. One of the major limitations of these inactivated vaccines is the time taken to develop a protective response in vaccinated birds. In the present study, we aimed to formulate an inactivated oil-based ND vaccine incorporated with lipopolysaccharide (LPS) that stimulates the early onset innate response to inactivated vaccines via proinflammatory cytokine production. Five groups of 21-day old SPF chicks were reared in isolators and were treated as follows: G1: Montanoid ISA71 adjuvanted NDV vaccinated group, G2: LPS and Montanoid ISA71 adjuvanted NDV vaccinated group, G3: LPS and Montanoid ISA71 with phosphate buffer saline received group and two non-vaccinated control groups. NDV specific antibodies and cell mediated immune responses were evaluated by hemagglutination inhibition and lymphocyte proliferation tests, respectively. Transcriptional responses of the TLR4, IFN-γ and IL-2 genes were analyzed in peripheral blood mononuclear cells (PBMCs) following vaccination by qRT-PCR. Protection % was determined after challenge with a lethal strain of NDV 106 EID50/0.5 ml. Viral shedding was assessed on oropharyngeal swabs by qRT-PCR and infectivity titration on SPF-ECE. The results revealed that the incorporation of LPS with ISA71 in the oil-based ND vaccine induced a synergistic response confirmed by significant humoral and lymphoproliferative responses with a significant increase in Th1 cytokine transcripts. The simultaneous use of both adjuvants in G2 demonstrated complete protection and a significant reduction in viral shedding compared to the ISA71-adjuvated ND vaccine in G1, which conferred 90 % protection.

The haemagglutinin-neuraminidase protein of velogenic Newcastle disease virus enhances viral infection through NF-κB-mediated programmed cell death.

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.

Use of live attenuated recombinant Newcastle disease virus carrying avian paramyxovirus 2 HN and F protein genes to enhance immune responses against species A rotavirus VP6 protein.

Numerous infectious diseases in cattle lead to reductions in body weight, milk production, and reproductive performance. Cattle are primarily vaccinated using inactivated vaccines due to their increased safety. However, inactivated vaccines generally result in weaker immunity compared with live attenuated vaccines, which may be insufficient in certain cases. Over the last few decades, there has been extensive research on the use of the Newcastle disease virus (NDV) as a live vaccine vector for economically significant livestock diseases. A single vaccination dose of NDV can sufficiently induce immunity; therefore, a booster vaccination dose is expected to yield limited induction of further immune response. We previously developed recombinant chimeric NDV (rNDV-2F2HN), in which its hemagglutinin-neuraminidase (HN) and fusion (F) proteins were replaced with those of avian paramyxovirus 2 (APMV-2). In vitro analysis revealed that rNDV-2F2HN expressing human interferon-gamma had potential as a cancer therapeutic tool, particularly for immunized individuals. In the present study, we constructed rNDV-2F2HN expressing the bovine rotavirus antigen VP6 (rNDV-2F2HN-VP6) and evaluated its immune response in mice previously immunized with NDV. Mice primarily inoculated with recombinant wild-type NDV expressing VP6 (rNDV-WT-VP6), followed by a booster inoculation of rNDV-2F2HN-VP6, showed a significantly stronger immune response than that in mice that received rNDV-WT-VP6 as both primary and booster inoculations. Therefore, our findings suggest that robust immunity could be obtained from the effects of chimeric rNDV-2F2HN expressing the same or a different antigen of a particular pathogen as a live attenuated vaccine vector.

A time series transcriptome profiling of host cell responses to Newcastle disease virus infection.

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.

Spillover of Newcastle disease virus to Himalayan Griffon vulture: a possible food-based transmission.

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.

Comparison of HVT-ND recombinant and convection-based Newcastle disease vaccination programs in the protection against the genotype VII NDV challenges: an experimental study.

Newcastle disease virus (NDV) belongs to the Avulavirus genus and Paramyxoviridae family virus that causes acute, highly infectious Newcastle disease in poultry. The two proteins of haemagglutinin neuraminidase (HN) and fusion (F) are key virulence factors with an important role in its immunogenicity. Genotype VII NDV is still among the most serious viral hazards to the poultry industry worldwide. In this study, a commercial vector vaccine (HVT-NDV) was evaluated compared to the conventional vaccination strategy against Iranian genotype VII. This experiment showed that the group receiving the conventional vaccination strategy had higher antibodies, fewer clinical signs, and lower viral loads in tracheal swabs and feces. Also, two vaccine groups showed significant difference, which could have resulted from two extra vaccine doses in the conventional group. However, except for antibody levels in commercial chickens in the Iran new-generation vaccine, this difference was minor. Further, both groups showed 100% protection in the challenge study. Despite the phylogenetic gap between the NDV-F gene placed in the vector vaccine and the challenge virus (genotypes I and VII, respectively), the rHVT-NDV vaccine offered strong clinical protection and decreased challenge virus shedding considerably.

Thermostable vacuum foam dried Newcastle disease vaccine: Process optimization and pilot-scale study.

Vacuum foam drying (VFD) has been shown to improve the thermostability and long-term shelf life of Newcastle Disease Virus (NDV). This study optimized the VFD process to improve the shelf life of NDV at laboratory-scale and then tested the optimized conditions at pilot-scale. The optimal NDV to T5 formulation ratio was determined to be 1:1 or 3:2. Using the 1:1 virus to formulation ratio, the optimal filling volumes were determined to be 13-17% of the vial capacity. The optimized VFD process conditions were determined to be at a shelf temperature of 25℃ with a minimum overall drying time of 44 h. The vaccine samples prepared using these optimized conditions at laboratory-scale exhibited virus titer losses of ≤ 1.0 log10 with residual moisture content (RMC) below 3%. Furthermore, these samples were transported for 97 days around China at ambient temperature without significant titer loss, thus demonstrating the thermostability of the NDV-VFD vaccine. Pilot-scale testing of the NDV-VFD vaccine at optimized conditions showed promising results for up-scaling the process as the RMC was below 3%. However, the virus titer loss was slightly above 1.0 log10 (approximately 1.1 log10). Therefore, the NDV-VFD process requires further optimization at pilot scale to obtain a titer loss of ≤ 1.0 log10. Results from this study provide important guidance for possible industrialization of NDV-VFD vaccine in the future. KEY POINTS: • The process optimization and scale-up test of thermostable NDV vaccine prepared through VFD is reported for the first time in this study. • The live attenuated NDV-VFD vaccine maintained thermostability for 97 days during long distance transportation in summer without cold chain conditions. • The optimized NDV-VFD vaccine preparations evaluated at pilot-scale maintained acceptable levels of infectivity after preservation at 37℃ for 90 days, which demonstrated the feasibility of the vaccine for industrialization.

Alpha-sitosterol: a new antiviral agent produced by Streptomyces misakiensis and its potential activity against Newcastle disease virus.

BACKGROUND: Newcastle Disease Virus (NDV) causes severe economic losses in the poultry industry worldwide. Hence, this study aimed to discover a novel bioactive antiviral agent for controlling NDV. Streptomyces misakiensis was isolated from Egyptian soil and its secondary metabolites were identified using infrared spectroscopy (IR), gas chromatography-mass spectrometry (GC-MS), and nuclear magnetic resonance (NMR) spectroscopy. The inhibitory activity of bioactive metabolite against NDV were examined. Three experimental groups of 10-day-old specific pathogen-free embryonated chicken eggs (SPF-ECEs), including the bioactive metabolite control group, NDV control positive group, and α-sitosterol and NDV mixture-treated group were inoculated. RESULTS: α-sitosterol (Ethyl-6-methylheptan-2-yl]-10,13-dimethyl-dodecahydro-1H-cyclopenta[a]phenanthren-3-ol), a secondary metabolite of S. misakiensis, completely inhibited hemagglutination (HA) activity of the NDV strain. The HA activity of the NDV strain was 8 log2 and 9 log2 for 0.5 and 0.75% RBCs, respectively. The NDV HA activity for the two concentrations of RBCs was significantly (P < 0.0001) inhibited after α-sitosterol treatment. There was a significant (P < 0.0001) decrease in the log 2 of HA activity, with values of - 0.500 (75%, chicken RBCs) before inoculation in SPF-ECEs and - 1.161 (50%, RBCs) and - 1.403 (75%, RBCs) following SPF-ECE inoculation. Compared to ECEs inoculated with NDV alone, the α-sitosterol-treated group showed improvement in histological lesion ratings for chorioallantoic membranes (CAM) and hepatic tissues. The CAM of the α-sitosterol- inoculated SPF-ECEs was preserved. The epithelial and stromal layers were noticeably thicker with extensive hemorrhages, clogged vasculatures, and certain inflammatory cells in the stroma layer in the NDV group. However, mild edema and inflammatory cell infiltration were observed in the CAM of the treated group. ECEs inoculated with α-sitosterol alone showed normal histology of the hepatic acini, central veins, and portal triads. Severe degenerative alterations, including steatosis, clogged sinusoids, and central veins, were observed in ECEs inoculated with NDV. Mild hepatic degenerative alterations, with perivascular round cell infiltration, were observed in the treated group. CONCLUSION: To the best of our knowledge, this is the first study to highlight that the potentially bioactive secondary metabolite, α-sitosterol, belonging to the terpene family, has the potential to be a biological weapon against virulent NDV. It could be used for the development of innovative antiviral drugs to control NDV after further clinical investigation.

Genomic Regions and Candidate Genes Affecting Response to Heat Stress with Newcastle Virus Infection in Commercial Layer Chicks Using Chicken 600K Single Nucleotide Polymorphism Array.

Heat stress results in significant economic losses to the poultry industry. Genetics plays an important role in chickens adapting to the warm environment. Physiological parameters such as hematochemical parameters change in response to heat stress in chickens. To explore the genetics of heat stress resilience in chickens, a genome-wide association study (GWAS) was conducted using Hy-Line Brown layer chicks subjected to either high ambient temperature or combined high temperature and Newcastle disease virus infection. Hematochemical parameters were measured during three treatment phases: acute heat stress, chronic heat stress, and chronic heat stress combined with NDV infection. Significant changes in blood parameters were recorded for 11 parameters (sodium (Na+, potassium (K+), ionized calcium (iCa2+), glucose (Glu), pH, carbon dioxide partial pressure (PCO2), oxygen partial pressure (PO2), total carbon dioxide (TCO2), bicarbonate (HCO3), base excess (BE), and oxygen saturation (sO2)) across the three treatments. The GWAS revealed 39 significant SNPs (p < 0.05) for seven parameters, located on Gallus gallus chromosomes (GGA) 1, 3, 4, 6, 11, and 12. The significant genomic regions were further investigated to examine if the genes within the regions were associated with the corresponding traits under heat stress. A candidate gene list including genes in the identified genomic regions that were also differentially expressed in chicken tissues under heat stress was generated. Understanding the correlation between genetic variants and resilience to heat stress is an important step towards improving heat tolerance in poultry.

Rescue of Recombinant Newcastle Disease Virus Expressing Heterologous Genes.

Reverse genetics allows for the generation of recombinant infectious viruses from viral sequences or complete viral genomes cloned into plasmids. Using reverse genetics, it is then possible to introduce changes in the genome of infectious viruses for multiple applications.Newcastle disease virus (NDV) is a non-segmented, negative-sense RNA virus that has been amenable to manipulation by reverse genetics for more than two decades. Since then, recombinant NDVs have been extensively used as viral vectors to express heterologous proteins. We describe the key steps required to design and introduce an additional transcription unit in the genome of the Newcastle disease virus for the efficient expression of a heterologous gene.

Newcastle viral disease causation web correlations with laying hen productivity.

Environmental conditions profoundly impact the health, welfare, and productivity of laying hens in commercial poultry farming. We investigated the association between microclimate variations, production indices, and histopathological responses to accidental Newcastle disease virus (NDV) infection within a controlled closed-house system. The study was conducted over seven months in a laying hen facility in Cairo, Egypt. Microclimate measurements included temperature, relative humidity (RH%), air velocity (AV), and the temperature humidity index (THI) that were obtained from specific locations on the front and back sides of the facility. Productivity indices, including the egg production percentage (EPP), egg weight (EW), average daily feed intake, and feed conversion ratio, were assessed monthly. During an NDV outbreak, humoral immune responses, gross pathology, and histopathological changes were evaluated. The results demonstrated significant (p < 0.05) variations in EPP and EW between the front and back sides except in April and May. AV had a significant (p = 0.006) positive effect (Beta = 0.346) on EW on the front side. On the back side, AV had a significant (p = 0.001) positive effect (Beta = 0.474) on EW, while it negatively influenced (p = 0.027) EPP (Beta = - 0.281). However, temperature, RH%, and THI had no impact and could not serve as predictors for EPP or EW on either farm side. The humoral immune response to NDV was consistent across microclimates, highlighting the resilience of hens. Histopathological examination revealed characteristic NDV-associated lesions, with no significant differences between the microclimates. This study underscores the significance of optimizing microclimate conditions to enhance laying performance by providing tailored environmental management strategies based on seasonal variations, ensuring consistent airflow, particularly near cooling pads and exhaust fans, and reinforcing the importance of biosecurity measures under field challenges with continuous monitoring and adjustment.

Thermostability study of virulent Newcastle disease viruses isolated in Southern Angola.

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.

Newcastle disease virus: the past and current situation in Indonesia.

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.

The Application of Newcastle Disease Virus (NDV): Vaccine Vectors and Tumor Therapy.

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.

A review of current knowledge on avian Newcastle infection in commercial poultry in the Kingdom of Saudi Arabia.

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.

In vivo challenge studies on vaccinated chickens indicate a virus genotype mismatched vaccine still offers significant protection against NDV.

Although commercial vaccines against Newcastle Disease have been available for decades, outbreaks still occur in the face of vaccination Further vaccination may accelerate viral evolution resulting in a further reduction in vaccine efficacy. A key question is whether genotype-matched vaccines can confer better protection against contemporary type 1 Avian Paramyxoviruses. To assess this, an in vivo vaccine-challenge study was undertaken to assess protection afforded by 'genotype-matched' and commercial vaccine formulations. Groups of chickens were vaccinated twice (prime-boost) with an inactivated preparation of either La Sota Clone 30, AV632-chicken-Cyprus-13 (genotype VII.2), or mock vaccine, and later challenged with virulent AV632-chicken-Cyprus-13. Post vaccinal serological responses differed, although both vaccination/challenge groups showed similar levels of clinical protection compared to the unvaccinated group, where 100 % mortality was observed. Shedding was significantly reduced in the vaccinated groups compared to the unvaccinated group. Virus dissemination in the tissues of vaccinated birds was comparable, but onset of infection was delayed. Two mutations were observed in the HN gene of the heterologous vaccine group; H199N and I192M, the latter thought to be associated with increased fusogenic potential. These data demonstrate that existing vaccine formulations confer similar levels of clinical protection to contemporary strains and that the antigenic heterogeneity of circulating strains does not impact upon shedding profiles in immunised birds. In conclusion, the ability of virulent APMV-1 to cause disease in vaccinated flocks is unlikely to be the result of antigenic mismatch alone, and other factors likely contribute to vaccination failure and breakthrough.

Genomic Diversity and Geographic Distribution of Newcastle Disease Virus Genotypes in Africa: Implications for Diagnosis, Vaccination, and Regional Collaboration.

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.

Molecular characteristics and phylogenetic analysis of pigeon paramyxovirus type 1 isolates from pigeon meat farms in Shanghai (2009-2012).

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.