Search Results (133)

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

Henipaviruses are emerging zoonotic viruses that have caused deadly outbreaks in humans and livestock across several regions of the world. The fusion (F) protein of henipaviruses plays a critical role in viral entry into host cells and represents a key determinant of viral pathogenicity. This review provides a comprehensive analysis of current knowledge regarding trafficking, activation, as well as the role in particle assembly, of henipavirus F proteins. We discuss the unique characteristics of henipavirus F proteins compared to other paramyxovirus fusion proteins, with particular emphasis on their distinctive trafficking and activation mechanisms. Attention is also given to novel henipaviruses that have been detected in hosts other than bats, namely rodents and shrews. These viruses are sufficiently different that the International Committee on Taxonomy of Viruses has proposed a new genus for them, the Parahenipaviruses. We discuss how variations in F protein characteristics between Henipaviruses, Parahenipaviruses, and yet-unclassified henipa-like viruses might influence their trafficking and activation. Understanding these molecular mechanisms is crucial for developing effective therapeutic strategies against henipavirus infections and for predicting the emergence of novel henipavirus strains with pandemic potential. Full article

Nipah virus (NiV), a highly lethal zoonotic paramyxovirus, displays strain-specific pathogenicity, yet the molecular basis for this divergence remains elusive. Here, we identify N6-methyladenosine (m6A) modification as a pivotal regulator of NiV replication. Higher m6A methylation levels on viral genomic RNA and mRNAs are associated with the increased virulence observed in the NiV-Malaysia (NiV-M) strain compared to NiV-Bangladesh (NiV-B). Underlying this phenomenon, NiV infection orchestrates a reprogramming of the host m6A machinery by downregulating the methyltransferase METTL3 and the demethylase ALKBH5, while concurrently upregulating m6A reader proteins YTHDF1-3. Both METTL3 and ALKBH5 bind directly to NiV RNA, with METTL3 installing m6A to promote viral replication and ALKBH5 removing them to inhibit it. Strikingly, pharmacological inhibition of m6A modification markedly attenuates NiV replication in vitro and in vivo, underscoring the therapeutic potential of targeting the m6A pathway. Our study establishes m6A as a key determinant of NiV pathogenicity and provides a paradigm for host-directed antiviral strategies against high-risk RNA viruses. Full article

Nipah virus (NiV) is a highly pathogenic paramyxovirus characterized by zoonotic infection, high mortality, and a lack of effective treatment, posing a serious threat to global public health security. Currently, it still lacks specific treatments or approved vaccines, and is listed as a potential pandemic threat pathogen by the World Health Organization. This paper systematically reviews the core progress and challenges of NiV investigation, with a focus on the development of animal models, vaccine development strategies, treatment strategy, and bottlenecks in translational medicine. Additionally, we discuss the strengths and limitations of existing animal models, including ferrets, hamsters, mice, and non-human primates (NHPs), and assess advances in vaccine platforms such as viral vectors, subunit vaccines, and mRNA-based vaccine candidates. The paper critically reviews the challenges facing translational research, conservation correlates, and outbreak preparedness, while also providing future research directions for pandemic preparedness and public health security strategies. 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

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

Pigeon Newcastle disease (ND) is the most common viral infectious disease in the pigeon industry, caused by pigeon paramyxovirus type 1 (PPMV-1), a variant of chicken-origin Newcastle disease virus (NDV). Previous studies have identified significant amino acid differences between PPMV-1 and chicken-origin NDV at positions 347 and 349 in the hemagglutinin–neuraminidase (HN) protein, with PPMV-1 predominantly exhibiting glycine (G) at position 347 and glutamic acid (E) at position 349, while most chicken-origin NDVs show E at position 347 and aspartic acid (D) at position 349. However, the impact of these amino acid substitutions remains unclear. In this study, we generated a recombinant virus, NT-10-G347E/E349D, by introducing the G347E and E349D dual mutations into a PPMV-1 strain NT-10 using reverse genetics. The biological characteristics of NT-10 and NT-10-G347E/E349D were compared both in vitro and in vivo. In vitro, the G347E and E349D dual mutations reduce NT-10′s replication and neuraminidase activity in pigeon embryo fibroblast (PEF) cells while enhancing both in chicken embryo fibroblast (CEF) cells. Additionally, these mutations decrease NT-10′s binding affinity to the α-2,6 sialic acid receptor while significantly increasing its affinity for the α-2,3 receptor. In vivo, NT-10-G347E/E349D exhibited reduced pathogenicity in pigeons but increased pathogenicity in chickens compared to the parental NT-10 strain. The mutations also reduced the pigeon-to-pigeon transmission of NT-10 but enhanced its transmission from pigeons to chickens. Notably, significant antigenic differences were observed between NT-10 and NT-10-G347E/E349D, as an inactivated vaccine based on NT-10 provided full protection against NT-10 challenge in immunized pigeons but only 67% mortality protection against NT-10-G347E/E349D. Overall, these findings underscore the critical role of amino acids at positions 347 and 349 in PPMV-1 infection, pathogenicity, and transmission, providing a theoretical foundation for the scientific prevention and control of PPMV-1. Full article

Background: Pigeon paramyxovirus type 1 (PPMV-1) is a significant pathogen affecting pigeon populations globally. The commonly used La Sota vaccine provides limited protection due to antigenic divergence from circulating PPMV-1 strains. An antigenically matched vaccine is needed to address this challenge. Methods: An attenuated aTJ strain was developed through reverse genetics by modifying the F protein cleavage site of the virulent TJ-WT strain. Pigeons were immunized twice with the aTJ strain via eyedrop and intranasal routes, followed by a challenge with a virulent PPMV-1 strain ten days after the booster immunization. Results: The attenuated aTJ strain induced robust serum antibody titers post-booster immunization, and vaccinated pigeons showed strong protection upon challenge, with significantly reduced morbidity, mortality, and viral shedding compared to controls. Conclusions: These findings suggest that the aTJ strain is a promising candidate for the promotion of PPMV-1 prevention and control, emphasizing the importance of antigenic matching in optimizing vaccine efficacy. Full article

Newcastle disease virus (NDV), known as avian paramyxovirus-1, poses a significant threat to poultry production worldwide. Vaccination currently stands as the most effective strategy for Newcastle disease control. However, the mesogenic vaccine strain Mukteswar has been observed to evolve into a velogenic variant JS/7/05/Ch during poultry immunization. Here, we aimed to explore the mechanisms underlying virulence enhancement of the two viruses. Pathogenically, JS/7/05/Ch mediated stronger virulence and pathogenicity in vivo compared to Mukteswar. Comparative transcriptome analysis revealed 834 differentially expressed genes (DEGs), comprising 339 up-regulated and 495 down-regulated genes, in the spleen, and 716 DEGs, with 313 up-regulated and 403 down-regulated genes, in the thymus. Gene Ontology (GO) analysis indicated that these candidate targets primarily participated in cell and biological development, extracellular part and membrane composition, as well as receptor and binding activity. Furthermore, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis unveiled a substantial portion of candidate genes predominantly involved in cellular processes, environmental information processing, metabolism, and organismal systems. Additionally, five DEGs (TRAT1, JUP, LPAR4, CYB561A3, and CXCR5) were randomly identified through RNA-seq analysis and subsequently confirmed via quantitative real-time polymerase chain reaction (qRT-PCR). The findings revealed a marked up-regulation in the expression levels of these DEGs induced by JS/7/05/Ch compared to Mukteswar, with CYB561A3 and CXCR5 exhibiting significant increases. The findings corroborated the sequencing accuracy, offering promising research directions. Taken together, we comprehensively evaluated transcriptomic alterations in chicken immune organs infected by NDV strains of diverse virulence. This study establishes a basis and direction for NDV virulence research. Full article

We utilized a pan-viral capture sequencing assay, VirCapSeq-VERT, to assess viral diversity in rodents from the Eastern Province of Zambia as a model for pre-pandemic viral reservoir surveillance. We report rodent adeno-, parvo-, paramyxo-, and picornaviruses that represent novel species or isolates, including murine adenovirus 4, two additional species in the genus Chaphamaparvovirus, two paramyxoviruses distantly related to unclassified viruses in the genus Jeilongvirus, and the first Aichivirus A sequence identified from rodents in Africa. Our results emphasize the importance of rodents as a reservoir for potential zoonotic viruses. Full article

Newcastle disease, which affects poultry and is endemic in many nations across the world, is caused by Avian Paramyxovirus-1 (APMV-1). This experimental study was conducted from January to June 2021 at the National Veterinary Institute (NVI) to evaluate the virus viability and antibody titer of Newcastle disease vaccines (Hichner’s B1, Lasota, and ThermostableI2) stored at different temperature storage conditions. Chickens (12 treatment groups and 1 control group) were vaccinated and challenged with the virulent ND virus (0.5 × 10^6.5 embryonic lethal dose fifty (ELD₅₀)). The immune responses (antibody titers) of chickens were evaluated using hemagglutination (HA) and hemagglutination inhibition (HI) assays. The Newcastle disease vaccines (Hachiner’s B1 (ND-HB1), ND-Lasota, and ND-Thermostable I2) stored at +4 °C HI-induced antibody titers of 151 (±103.3), 136 (±53.4), and 145 (±91) on day 14, respectively, whereas on day 21, they increased to 160 (±82) for ND-HB1 and 144 (±74.5) for ND-Lasota. ND-Thermostable I2 showed a decrement to 133 (±44.8). All three vaccines stored at different temperature storage conditions (+4, +23, and +30 °C) used in this experiment induced antibody titers greater than 128 on day 28 post-vaccination, except the Newcastle disease vaccine Thermostable I2 stored at +30 °C. The vaccines collected from private veterinary drugstores (customer vaccines Hachiner’s B1 and ND-Thermostable I2) used in this experiment induced very low antibody titers, less than 128 antibody titers, from days 14 to 21. Statistically significant induced mean antibody titers were observed for chickens that received vaccines stored at different temperature storage conditions for 72 h (p < 0.05), except for the ND-HB1 mean HI-induced antibody titer at days 7 and 28. Further, vaccine protection was confirmed by inoculation of both the vaccinated (treatment groups) and control groups by the virulent ND virus, where the control group started dying three days post-challenge but all chicks that received the vaccines survived. Overall, this study showed the impact of temperature storage conditions on the antibody titer and their effect on the titer of the viable virus in the vaccine, and thereby its protective capacity, warranting appropriate cold chain management of the vaccines along the value chain. Full article

Pigeon paramyxovirus serotype 1 (PPMV-1), an antigenic and host variant of avian paramyxovirus Newcastle disease virus (NDV), primarily originating from racing pigeons, has become a global panzootic. Egypt uses both inactivated PPMV-1 and conventional NDV vaccines to protect pigeons from disease and mortality. However, the impact of prevalent strains and the effectiveness of available vaccines in pigeons in Egypt are unclear. This study investigates the virulence of PPMV-1 (Pigeon/Egypt/Sharkia-19/2015/KX580988) and evaluates available paramyxovirus vaccines in protecting pigeons against a PPMV-1 challenge. Ten-day-old specific-pathogen-free (SPF) embryonated chicken eggs infected with this strain exhibited a mean death time (MDT) of 86.4 ± 5.88 h. The intracerebral pathogenicity index (ICPI) in day-old chickens was 0.8, while pigeons experienced an ICPI of 0.96 and an intravenous pathogenicity index (IVPI) of 2.11. These findings classify the strain as virulent and velogenic. Experimental infection of pigeons with this PPMV-1 strain at 10⁶ EID₅₀/0.1 mL resulted in a 62.5% mortality rate, displaying nervous and enteric distress. The virus caused extensive lesions in visceral organs, with strong immunohistochemistry signals in all examined organs, indicating the systemic spread of the virus concurrent to its neurotropic and viscerotropic tropism. Furthermore, vaccination using an inactivated PPMV-1 and live NDV LaSota vaccine regimen protected 100% of pigeons against mortality, while with a single NDV LaSota vaccine, it was 62.5%. The PPMV alone or combined with NDV LaSota induced protective levels of haemagglutination inhibition (HI) antibody titres and reduced virus shedding from buccal and cloacal cavities. Based on generalised linear gamma model analysis, both PPMV-1 and NDV LaSota are antigenically comparable by HI. These findings suggest that using both inactivated PPMV-1 (G-VI) and live attenuated NDV (LaSota) vaccines is an effective prophylactic regimen for preventing and controlling PPMV-1 and NDV in pigeons, thereby reducing the risk of interspecies transmission. Full article

Pigeon Newcastle disease, caused by pigeon paramyxovirus type 1 (PPMV-1), is a significant infectious disease in pigeons that can result in substantial mortality and poses a severe threat to the pigeon industry. The rapid and accurate onsite diagnosis of pigeon disease is crucial for timely diagnosis and the implementation of effective prevention and control measures. In this study, we established a rapid detection method for PPMV-1 based on recombinase-aided amplification (RAA) and CRISPR/Cas12a. The RAA primers target the conserved regions of the L gene for preamplification in clinical nucleic acid samples, followed by CRISPR/Cas12a detection of the target gene. Visualization could be achieved by combination with a lateral flow dipstick (LFD). This method demonstrated high specificity, showing no cross-reactivity with non-PPMV-1 samples. The sensitivity of the method assessed by fluorescence analysis reached 10⁰ copies/µL, and when it was combined with an LFD, the sensitivity was 10³ copies/µL. The constructed RAA-CRISPR/Cas12a-LFD visual detection method was applied to clinical sample testing and was found to enable the rapid and accurate detection of swab samples and tissue specimens. Its sensitivity was consistent with the current gold standard, quantitative real-time PCR results. The RAA-CRISPR/Cas12a-LFD detection method we developed provides a novel approach for the rapid, simple, precise, and specific onsite diagnosis of pigeon Newcastle disease. Full article

A novel jeilongvirus was identified through next-generation sequencing in cell cultures inoculated with spleen and kidney extracts. The spleen and kidney were obtained from a Peromyscus gossypinus rodent (cotton mouse) found dead in the city of Gainesville, in North-Central Florida, USA. Jeilongviruses are paramyxoviruses of the subfamily Orthoparamyxovirinae that have been found in bats, cats, and rodents. We designated the virus we discovered as Gainesville rodent jeilong virus 1 (GRJV1). Preliminary results indicate that GRJV1 can complete its life cycle in various human, non-human primate, and rodent cell lines, suggesting that the virus has a generalist nature with the potential for a spillover event. The early detection of endemic viruses circulating within hosts in North-Central Florida can significantly enhance surveillance efforts, thereby bolstering our ability to monitor and respond to potential outbreaks effectively. Full article

The virulent form of Avian paramyxovirus-1 (APMV-1), commonly known as Newcastle Disease Virus (NDV), is a pathogen with global implications for avian health, affecting both wild and domestic bird populations. In Pakistan, recurrent Newcastle Disease (caused by NDV) outbreaks have posed significant challenges to the poultry industry. Extensive surveillance in Pakistan over 20 years has demonstrated a dynamic genetic diversity among circulating APMV-1 strains, emphasizing the potential necessity for customized vaccination strategies and continuous surveillance. In this study, 13 APMV-1-positive isolates harboring four different APMV-1 genotypes circulating throughout Pakistan were identified. These included the highly virulent genotypes VII and XIII, genotype XXI, commonly associated with Columbiformes, and genotype II, hypothesized to have been detected following vaccination. These findings underscore the intricate interplay of mutational events and host-immune interactions shaping the evolving NDV landscape. This study advances our understanding of the evolutionary dynamics of APMV-1 in Pakistan, highlighting the need for tailored vaccination strategies and continuous surveillance to enable effective APMV-1 management in avian populations, further emphasizing the importance of globally coordinated strategies to tackle APMV-1, given its profound impact on wild and domestic birds. Full article