Search Results (251)

Glioblastoma (GBM) remains one of the most aggressive and treatment-resistant brain tumors, necessitating novel therapeutic approaches. Oncolytic treatments, particularly oncolytic viruses (OVs), have emerged as promising candidates by selectively infecting and lysing tumor cells while stimulating anti-tumor immunity. Various virus-based therapies are under investigation, including genetically engineered herpes simplex virus (HSV), adenovirus, poliovirus, reovirus, vaccinia virus, measles virus, and Newcastle disease virus, each exploiting unique tumor-selective mechanisms. While some, such as HSV-based therapies including G207 and Delytact^TM, have demonstrated clinical progress, significant challenges persist, including immune evasion, heterogeneity in patient response, and delivery barriers due to the blood–brain barrier. Moreover, combination strategies integrating OVs with immune checkpoint inhibitors, chemotherapy, and radiation are promising but require further clinical validation. Non-viral oncolytic approaches, such as tumor-targeting bacteria and synthetic peptides, remain underexplored. This review highlights current advancements while addressing critical gaps in the literature, including the need for optimized delivery methods, better biomarker-based patient stratification, and a deeper understanding of GBM’s immunosuppressive microenvironment. Future research should focus on enhancing OV specificity, engineering viruses to deliver therapeutic genes, and integrating OVs with precision medicine strategies. By identifying these gaps, this review provides a framework for advancing oncolytic therapies in GBM treatment. Full article

Viral oncolysis is considered a promising cancer treatment method because of its good tolerability and durable anti-tumor effects. Compared with other oncolytic viruses, Newcastle disease virus (NDV) has some distinct advantages. As an RNA virus, NDV does not recombine with the host genome, making it safer compared with DNA viruses and retroviruses; NDV can induce syncytium formation, allowing the virus to spread among cells without exposure to host neutralizing antibodies; and its genome adheres to the hexamer genetic code rule (genome length as a multiple of six nucleotides), ensuring accurate replication, low recombination rates, and high genetic stability. Although wild-type NDV has a killing effect on various tumor cells, its oncolytic effect and working mechanism are diverse, increasing the complexity of generating engineered oncolytic viruses with NDV. This study aims to employ whole-genome CRISPR-Cas9 knockout screening and RNA sequencing to identify putative key regulatory factors involved in the interaction between NDV and human colon cancer HCT116 cells and map their global interaction networks. The results suggests that NDV infection disrupts cellular homeostasis, thereby exerting oncolytic effects by inhibiting cell metabolism and proliferation. Meanwhile, the antiviral immune response triggered by NDV infection, along with the activation of anti-apoptotic signaling pathways, may be responsible for the limited oncolytic efficacy of NDV against HCT116 cells. These findings not only enhance our understanding of the oncolytic mechanism of NDV against colonic carcinoma but also provide potential strategies and targets for the development of NDV-based engineered oncolytic viruses. Full article

Background/Objectives: Prostate cancer is the second most common type of cancer diagnosed in men. Various treatments for this cancer, such as radiation therapy, surgery, and systemic therapy, can cause side effects in patients; therefore, there is a need to develop new treatment alternatives. One promising approach is virotherapy, which involves using oncolytic viruses (OVs), such as the recombinant Newcastle disease virus (rNDV). Methods: We used the lentogenic rNDV rLS1 strain (the control virus) as our backbone to develop two highly fusogenic rNDVs: rFLCF5nt (the parental virus) and rFLCF5nt-IFN-γ (rFLCF5nt expressing human interferon-gamma (IFN-γ)). We evaluated their oncolytic properties in a prostate cancer cell line (DU145). Results: The results showed the expression and stability of the IFN-γ protein, as confirmed using Western blotting after ten passages in specific pathogen-free chicken embryo eggs using the IFN-γ-expressing virus. Additionally, we detected a significantly high oncolytic activity in DU145 cells infected with the parental virus or the IFN-γ-expressing virus using MTS (a cell viability assay) and Annexin V-PE assays compared with the control virus (p < 0.0001 for both). Conclusions: In conclusion, our data show that IFN-γ-expressing virus can decrease cell viability and induce apoptosis in human prostate cancer in vitro. Full article

Newcastle disease virus (NDV) genotype VI from pigeon origin is an important causative agent for serious disease in pigeons. Although the biological characteristics of genotype VI NDV have been extensively studied, the understanding of the thermostability of this genotype is still incomplete. In this study, an NDV strain, designated P0506, was isolated from a diseased pigeon in China and classified as genotype VI. Phylogenetic analysis on the basis of the Fusion gene coding sequence indicated that P0506 belonged to sub-genotype VI.2.1.1.2.2 of class II. The thermostability may be a universal characteristic of genotype VI NDV. Thus, the thermostability of two strains, including P0506 identified in this study and P0713 identified previously, belonging to VI.2.1.1.2.2, and another previously isolated strain, P0813, in VI.2.1.1.2.1, was investigated. It was indicated that all three viruses presented resistance to heat treatment, but P0713 was more robust than P0813 and P0506. By constructing a series of HN protein mutants, amino acid residues at both residues 365 and 497 in HN protein were found to be involved in the heat resistance. Furthermore, the effects of residues 365 and 497 in HN protein on the thermostability of the virus were further evaluated by using recombinant viruses generated by the reverse genetic system. Our results showed that residue at position 365 in HN protein was the key thermostable determinant of sub-genotype VI.2.1.1.2.2 NDV. These findings will help us better understand the thermostable mechanism of NDV and serve as a foundation for the further development of novel thermostable vaccines. Full article

Wild waterbirds are circulating important RNA viruses, such as avian coronaviruses, avian astroviruses, avian influenza viruses, and avian paramyxoviruses. Waterbird migration routes cover vast territories both within and between continents. The breeding grounds of many species are in the Arctic, but research into this region is rare. This study reports the first Newcastle disease virus (NDV) detection in Arctic Russia. As a result of a five-year study (from 2019 to 2023) of avian paramyxoviruses and avian influenza viruses in wild waterbirds of the Taimyr Peninsula, whole-genome sequences of NDV and H3N8 were obtained. The resulting influenza virus isolate was phylogenetically related to viruses that circulated between 2021 and 2023 in Eurasia, Siberia, and Asia. All NDV sequences were obtained from the Herring gull, and other gull sequences formed a separate gull-like clade in the sub-genotype I.1.2.1, Class II. This may indirectly indicate that different NDV variants adapt to more host species than is commonly believed. Further surveillance of other gull species may help to test the hypothesis of putative gull-specific NDV lineage and better understand their role in the evolution and global spread of NDV. Full article

Newcastle disease, caused by virulent strains of avian paramyxovirus 1 (APMV-1), occurs globally and has significant social and economic impact. APMV-1 is a rapidly evolving RNA virus and is genetically divided into class I and class II with almost all virulent viruses being of class II. The considerable genetic diversity of the virus adds complexity to maintaining the high sensitivity and specificity of molecular detection assays. The current USDA’s fusion gene rRT-PCR assay was designed for class II APMV-1 isolates with an emphasis on early-2000s US strains. Assessment with globally circulating genotypes confirmed previously described lower sensitivity (sub-genotypes VII.1.1, VII.2) and identified absence of detection (genotype XIV). An additional forward primer and two probes were designed using a comprehensive complete fusion gene sequence database. The optimized multiplex assay detected genotype XIV and improved sensitivity for sub-genotypes VII.1.1 and VII.2, with maintained sensitivity for the remaining genotypes. No near-neighbors or APMV-1 of low virulence were detected. Using field and experimental clinical samples, both the specificity and sensitivity were determined to be 100%, compared to the current assay with 100% and 93%, respectively. The new assay identifies all known chicken virulent APMV-1 genotypes with the benefit of using an exogenous internal positive control, which monitors extraction efficiency and inhibitors. Full article

Background/Objectives: Despite the availability of Newcastle disease (ND) vaccines, outbreaks have continued to occur for more than six decades, with significant economic consequences for the global poultry industry. The variability of the Newcastle disease virus requires constant monitoring, detection of new cases, and studies of the origin of the pathogen. The aim of this study was to develop an inactivated ND vaccine using a topical strain with different adjuvants and to compare them for stability, harmlessness, immunogenicity, and efficacy. Methods: A phylogenetic study of the F-gene of the ND strain isolated in Kazakhstan was conducted. The strain, which was selected to create a vaccine for the prevention of the disease, was revealed to belong to genotype VII class II and uploaded to GenBank (NCBI). Two different adjuvants, Montanide ISA 70 VG and Montanide ISA 78 VG, were used to create the vaccine. Birds were vaccinated intramuscularly. Results: Evaluations of antibody titers in the vaccinated groups during the experiment showed that the vaccines induced adequate levels of antibodies to provide protection against the virulent virus. High antibody titers were observed in the hemagglutination inhibition assay (HAI) in the vaccinated groups as early as 14 days post-vaccination in 100% of birds. The average antibody titer in both vaccinated groups exceeded 7 log2, sufficient to prevent clinical signs. None of the vaccinated birds exhibited clinical signs following control infection, whereas unvaccinated birds developed clinical manifestations within three days post-infection, leading to 100% mortality. Conclusions: The vaccine developed using the epizootic topical strain is stable, harmless, immunogenic, and effective when challenged with a virulent ND virus strain at a dose of 105 EID_50/mL. Full article

The poultry industry is a critical source of affordable protein worldwide; however, it faces continuous threats from various poultry diseases that significantly impact public health, economic stability, and food security. Knowledge of and examination of the transmission routes, risk factors, and environmental survival characteristics of the most important pathogens affecting poultry populations, as well as the importance of strict biosecurity, are pivotal. Transmission routes are split into direct and vector-borne pathways, and indirect ways, which include infections via contaminated surfaces and vector-borne pathways, including insects and rodents. Avian influenza virus and Newcastle disease virus spread through respiratory droplets, and their transmission risk increases with increasing stocking density. While other pathogens (e.g., infectious bursal disease virus and Salmonella spp.), to persist long-term in the environments, for example, feed and litter, increasing the probability to persist long-term in the environments, for example, feed and litter, increasing the probability of infection. The long-term resilience of pathogens in multiple pathogens in various environmental conditions highlights the role of biosecurity, sanitation, and hygiene controls in preventing disease outbreaks. High stocking density in production systems, suboptimal ventilation, and inadequate biosecurity controls further increase transmission risks. This paper summarizes important disease transmissions and reinforces the need for strict biosecurity protocols and routine health monitoring to prevent the spread of pathogens within and beyond poultry facilities. These strategies can support safe poultry production, address growing global demand, and ensure food safety and public health. Full article

Newcastle disease viruses (NDVs) circulating among wild birds and poultry may differ in virulence. Some NDVs cause devastating outbreaks in chickens. The NDV/duck/Moscow/3639/2008 (d3639) strain was isolated from a wild duck. Its genome was sequenced (PP795281, GenBank) and the biological properties, specifically for infection in chicken and mice, were studied. Strain d3639 of genotype I.2 has an F protein cleavage site (112-GKQGRL-117) and a HN protein length (616 a.a.) of the lentogenic pathotype. It was tested, in comparison with the genotype II LaSota vaccine strain, for its immunogenicity and protective efficacy against a challenge with the velogenic NDV strain NDV/chicken/Moscow/6081/2022 (ch6081) of sub-genotype VII.1.1, the complete genome of which was also sequenced in this study (PP766718, GenBank). Both the d3639 and LaSota viruses did not induce clinical signs in chickens or mice. Single immunization was performed by inoculation through drinking water with the live virus. Inoculation protected the chickens during a subsequent challenge with velogenic ch6081 and significantly reduced shedding in feces. Double immunization was sufficient to achieve prolonged immunity and prevented the shedding of the velogenic virus after the challenge. Thus, this natural lentogenic d3639 virus possesses properties similar to the LaSota vaccine strain and can protect against sub-genotype VII.1.1 NDV. Full article

Newcastle disease virus (NDV) continues to present a significant challenge for vaccination due to its rapid evolution and the emergence of new variants. Although molecular and sequence data are now quickly and inexpensively produced, genetic distance rarely serves as a good proxy for cross-protection, while experimental studies to assess antigenic differences are time consuming and resource intensive. In response to these challenges, this study explores and compares several machine learning (ML) methods to predict the antigenic distance between NDV strains as determined by hemagglutination-inhibition (HI) assays. By analyzing F and HN gene sequences alongside corresponding amino acid features, we developed predictive models aimed at estimating antigenic distances. Among the models evaluated, the random forest (RF) approach outperformed traditional linear models, achieving a predictive accuracy with an R² value of 0.723 compared to only 0.051 for linear models based on genetic distance alone. This significant improvement demonstrates the usefulness of applying flexible ML approaches as a rapid and reliable tool for vaccine selection, minimizing the need for labor-intensive experimental trials. Moreover, the flexibility of this ML framework holds promise for application to other infectious diseases in both animals and humans, particularly in scenarios where rapid response and ethical constraints limit conventional experimental approaches. Full article

Background: An NDV-based vector has been used as a veterinary vaccine and, recently, as a human COVID-19 vaccine. However, data for the potential immune response against the vector in humans are scarce; therefore, it is important to evaluate the levels of antibodies produced. The HI assay is the gold standard for assessing the humoral response against NDV in poultry serum. Objective: Here, the objective was to validate the HI assay against the NDV-vectored vaccine to analyze antibodies in human serum. Methods: First, we standardized the conditions in human sera before validation. Results: The results for analytical performance in terms of selectivity, sensitivity, specificity, and positive and negative predictive values, as well as positive and negative diagnostic reliability, indicate that the assay is highly selective, allowing clear discrimination between positive and negative samples. Regarding repeatability and intermediate precision, we demonstrated that the assay has the precision to obtain consistent results, guaranteeing their reliability and truthfulness. Finally, the results regarding accuracy, linearity, and robustness indicate that the assay is accurate across the evaluated concentration intervals, with a linear correlation between low and high levels, and demonstrate that it is robust and consistent when serum–antigen interaction times are changed. Conclusions: We conclude that the suitability of the analytical method for its intended use is confirmed, guaranteeing the reliability of the results obtained under the established operating conditions. Full article

Paretic and paralyzing syndromes affecting wild birds are widely described in the literature, with outbreaks showing an increase in frequency and intensity worldwide during recent years. In the Iberian Peninsula, a paretic clinical picture without known etiology affecting mostly gulls has been reported during the last few decades. This paretic syndrome (PS) affects waterbirds and is characterized by a set of signs of ascendent flaccid paralysis, dyspnea, and diarrhea at different levels of severity. This study presents the first macro-analysis of some potential etiological PS agents in wild birds in southern Portugal. Other possible etiologies of PS related to nutritional deficiencies and environmental pollutants were not studied but are also discussed here. A total of 571 samples, belonging to 377 individuals with (n = 336) and without (n = 41) PS signs, have been tested for seven different toxins groups (botulinum neurotoxin (BoNT), paralytic shellfish toxins (PSTs), domoic acid (DA), anatoxin-a (ATX-a), cylindrospermopsin (CYN), tetrodotoxins (TTXs), and microcystins (MCs)) and three viral infections (gull adenovirus (GA), Newcastle disease virus (NVD), and highly pathogenic avian influenza viruses (HPAIV)). Of all the birds tested for botulinum neurotoxin, those with PS signs were positive (100%) and those without PS signs were negative (0%), confirming an association between PS and botulism. Some samples were positive for PSTs and MCs, but the prevalence in birds with PS signs was not significantly higher (2.5% and 5.3%, respectively) than in birds without signs (5.4% and 5.4%, respectively). Two birds without PS signs were positive for highly pathogenic avian influenza virus. The presence of the rest of the toxins and viruses was negative for all the samples tested. Our results support the relevant contribution of botulinum neurotoxin in the PS outbreaks observed in several species of aquatic birds in the last decades in southern Portugal, suggesting it could be one of the main causes of mortality in waterbirds. Full article

Mycoplasma, reticuloendotheliosis virus (REV), avian leukosis virus (ALV), chicken infectious anemia virus (CIAV), bovine polyomavirus (BPV), bovine viral diarrhea virus (BVDV), and porcine circovirus (PCV) are considered common contaminants in live veterinary vaccines against Newcastle disease virus (NDV), fowlpox virus (FPV), infectious bursal disease virus (IBDV), classical swine fever virus (CSFV), pseudorabies virus (PRV), and porcine reproductive and respiratory syndrome virus (PRRSV). In the past five years, Getah virus (GETV), an arbovirus affecting many farming mammals, was reported as a new contaminant in live PRRSV vaccines in two previous studies, which arouses our considerable interest. Therefore, in this paper, we aim to analyze and discuss the source, biological hazard, and genomic characteristics of these contaminating GETV strains further. Full article

Background: Middle East Respiratory Syndrome Coronavirus (MERS-CoV) causes severe respiratory illness in humans and currently lacks an approved vaccine. The Newcastle disease virus (NDV) vector is a well-established, safe, and effective platform for vaccine development. With recent advancements in stabilizing coronavirus spike proteins to enhance their antigenicity, this study aimed to determine whether modifications to the MERS-CoV spike protein could improve its presentation on NDV particles, allowing the resulting virus to be used as an inactivated vaccine. Methods: We codon-optimized the gene encoding the ectodomain of the MERS-CoV spike protein and incorporated modifications at the S1/S2 and S2’ cleavage sites, along with a proline substitution at residues V1060-L1061. This modified spike gene was inserted into the NDV genome to create the NDV-S_MERS virus. After purification and inactivation, the vaccine’s immunogenicity was assessed in mice. Results: Mice immunized with the inactivated NDV-S_MERS vaccine developed robust anti-spike IgGs, neutralizing antibodies, and cellular immune responses. The study demonstrated that modifications to the MERS-CoV spike protein were essential for its effective presentation on NDV particles. Additionally, the spike gene insert remained stable through five egg passages, confirming the vector’s stability. Conclusions: Engineering the MERS-CoV spike protein is crucial for its successful display on NDV particles. The strong immune responses elicited by the NDV-S_MERS vaccine in mice highlight that NDV is a promising, safe, and effective platform for MERS-CoV vaccination. Full article

Background: West Nile Virus [WNV] is a mosquito-borne flavivirus. It has spread globally, causing asymptomatic to severe neurological diseases in humans, with an increased risk in older adults and those with underlying conditions. This review examines WNV’s impact on pregnancy, focusing on maternal and neonatal symptoms and risks. Methods: This systematic review included primary studies from “PUBMED” and “SCOPUS” databases, as well as Google and Google Scholar, conducted in July 2024 using the appropriate keywords. This review adhered to PRISMA guidelines and utilized the Newcastle–Ottawa scale for bias assessment. Results: Seven primary studies were included in the systematic review. Fever was the predominating symptom, including neurological manifestations, respiratory symptoms, myalgia, weakness, nausea, vomiting, and rashes. Delivery, in most cases, progressed without any complications, while no infection was noted. Most of the neonates had a normal Apgar score, and their developmental functions did not seem to be affected. Even though, antibodies against WNV were detected in breast milk, no association with transmission to the neonate was observed. Conclusions: WNV infection is mostly associated with favorable outcomes during pregnancy. However, larger cohorts are needed to confirm our conclusions. Prompt diagnosis and public health surveillance are pivotal to eliminate disease transmission. Full article