Search Results (58)

The H9N2 avian influenza virus (AIV) is currently widespread globally and poses a serious threat to the poultry industry and public health; however, its global epidemiological characteristics and key molecular mutation patterns have not yet been systematically elucidated. Based on the NCBI Influenza Virus Resource Database, this study collected relevant data on the H9N2 AIV from around the world between 1966 and 2023. It conducted a comprehensive analysis of the geographic distribution of 11,933 strains, the temporal distribution of 11,824 strains, the host sources of 11,756 strains, and the genetic polymorphisms at key functional sites. The results showed that 90.14% of H9N2 AIV sequences in the dataset originated from Asia, with China contributing the largest number of sequences. The global sequence availability pattern underwent four phases: sporadic sequence availability, gradual increase, high sequence availability, and subsequent decline, with 2007–2018 representing a period of relatively high availability of publicly accessible sequences. Host analysis indicated that H9N2 AIV sequences were predominantly derived from poultry-related hosts, with chickens being the main host source in the dataset, and available sequences have also been reported from various mammals, including pigs and humans, as well as environmental media. Molecular analysis revealed that receptor-binding-related sites in the HA protein, such as Q226L and I155T, have become dominant variants, while mammalian-adaptive mutations such as PB2 E627K and D701N remain at low frequencies; M2 S31N is widely prevalent, whereas the detection rate of NA drug-resistance-associated mutations is low. This study systematically reveals the global distribution patterns of available H9N2 AIV sequences, host distribution characteristics, and key molecular mutation patterns of the H9N2 AIV, providing a scientific basis for cross-host transmission risk assessment, molecular surveillance, and targeted prevention and control. Full article

Highly pathogenic avian influenza H5N1 virus (H5N1 HPAIV) has long circulated in wild waterfowl and poultry and continues to cross species barriers, posing sustained threats to livestock productivity and public health. The 2024 outbreak of H5N1 HPAIV in dairy cattle across multiple U.S. states represents the first recognized large-scale transmission event of this virus in ruminants, reshaping our understanding of its host range and transmission ecology. This review summarizes recent advances in the epidemiology, virological characteristics, transmission, pathogenesis, surveillance, and control of dairy cattle-associated H5N1. The initial multistate outbreak was dominated by clade 2.3.4.4b genotype B3.13, whereas subsequent independent introductions of genotype D1.1 demonstrated that repeated avian-to-cattle spillover also contributes to the evolving outbreak ecology. A defining feature is efficient replication in bovine mammary epithelial cells, resulting in high viral titers in milk, supporting milk-associated exposure and milking-related contamination as plausible components of transmission, although the relative contribution of different routes remains unresolved. Infected cattle typically show reduced feed intake, a marked decline in milk production, abnormal milk, and mild systemic signs, whereas severe respiratory disease and mortality are uncommon. Mutations such as PB2-M631L, PA-K497R, and changes in NP and NS1 may promote replication and immune evasion in bovine cells, while genotype-specific PB2 adaptations highlight the potential for further mammalian adaptation. Human infections reported to date have been predominantly mild and associated with occupational exposure, with no evidence of sustained human-to-human transmission. Experimental vaccine studies have begun to demonstrate immunogenicity in cattle, although protection against mammary infection, viral shedding, and transmission remains to be established. Future priorities include clarifying mammary tropism and transmission dynamics, while strengthening diagnostics, farm biosecurity, vaccination, evaluating cattle vaccination strategies, and integrated One Health surveillance. Full article

The highly pathogenic H5 subtype avian influenza viruses (AIVs) pose persistent threats to the poultry industry and public health owing to their high lethality and pandemic potential. Migratory wild birds play a pivotal role in the global dissemination and genetic reassortment of the virus, serving as both natural reservoirs and long-distance vectors that drive its spatiotemporal spread. However, the extent and evolutionary drivers of antigenic divergence among H5 AIVs circulating in wild birds in East China remain poorly understood. Here, we aim to characterize the evolutionary dynamics and antigenic divergence of H5 AIVs isolated from wild birds in East China between 2013 and 2022. Whole-genome sequencing and phylogenetic analysis revealed that the isolates belonged to multiple clades, including 2.3.2.1 and 2.3.4.4, and encompassed the H5N1, H5N6, and H5N8 subtypes. Key amino acid site analysis showed that the glycosylation site patterns in the HA and NA proteins varied among clades, with some strains exhibiting gains or losses of glycosylation sites, while certain strains had acquired mutations associated with mammalian adaptation. Cross-hemagglutination inhibition (HI) assays combined with antigenic cartography demonstrated that the majority of the isolates were antigenically well-matched with the contemporaneous vaccine strains used in China, indicating that these vaccines effectively covered the predominant circulating antigenic variants at the time. Nevertheless, potential antigenic mismatches were still observed between some circulating strains and these vaccine strains. These findings suggest that wild birds in East China may contribute to the regional movement and diversification of H5 AIVs, highlighting the value of sustained surveillance for early warning and vaccine strain evaluation. Full article

H9N2 avian influenza viruses inherently carry cross-species transmission potential, making continuous surveillance critical for pandemic prevention. This study focused on monitoring the 2024 H9N2 epidemic in Jiangsu Province’s external environment, analyzing its molecular evolution and receptor binding properties, assessing cross-species transmission and pandemic risks, and investigating serological antibody levels across different human populations. Environmental samples were collected from live poultry markets, farms, slaughterhouses, and bird habitats across Jiangsu, screened via quantitative PCR (qPCR), with positive samples used for virus isolation and whole-genome sequencing. Receptor binding properties were tested by hemagglutination assay, and H9N2 antibody levels were measured in 370 occupationally exposed individuals and 240 non-exposed individuals using hemagglutination inhibition (HI) assays. Among the 5779 collected samples, 6.89% tested H9N2-positive, and 12 strains belonging to the Eurasian lineage Y280-like clade G57 genotype were successfully isolated. All strains carried the HA-Q226L mutation, with 11 showing preferential binding to human α-2,6 receptors and one strain possessing dual receptor binding capability. Internal genes harbored mammalian adaptation mutations, and M2 proteins contained mutations conferring complete resistance to amantadine-class antiviral drugs. Serological tests revealed antibody positive rates of 4.05% in exposed populations and 2.5% in non-exposed populations, with no statistically significant difference between groups. These findings confirm that Jiangsu’s circulating H9N2 viruses have acquired human receptor preference and mammalian adaptation, posing silent infection and pandemic risks. Enhanced surveillance and the development of candidate vaccine stockpiles are strongly recommended. Full article

H3N2 subtype avian influenza virus (AIV) is prevalent in poultry and wild birds and typically causes asymptomatic or mild respiratory infections. However, genetic reassortment between H3N2 and other AIV subtypes generates novel strains capable of crossing the species barrier, posing a threat to both poultry and public health. In this study, nine H3N2 AIVs were isolated from ducks in live poultry markets (LPMs) in Guangxi, southern China, during 2022–2024. Phylogenetic analysis revealed that all eight gene segments of the nine isolates were clustered within the Eurasian lineage, with internal genes derived from multiple subtypes, including H1, H2, H3, H4, H5, H6, H7, and H9. These findings indicate complex gene reassortment of H3N2 AIVs in Guangxi. Importantly, the PB2 genes of certain isolates were closely related to those of highly pathogenic H5 subtype viruses, suggesting that H3N2 AIVs may contribute internal genes to H5 viruses. Three representative isolates (LZD44, NND98, and NND100) were assessed for pathogenicity in SPF chickens and mice. All three strains successfully replicated in the respiratory tissues of both species. Notably, the LZD44 virus, which harbored the mammalian-adaptive mutations PB2-MVV and NP-I353V, presented significantly higher virulence in chickens and mice than the other two strains. These results demonstrate that H3N2 subtype AIVs are capable of replicating in certain tissues of chickens and mice without prior adaptation, underscoring a potential risk for cross-species transmission. Consequently, sustained surveillance of H3N2 subtype AIVs is essential to prevent the spillover of novel recombinants into the human population. Full article

Objective: The aim of this study was to characterize the epidemiological features and whole-genome characteristics of H5 subtype avian influenza viruses circulating in Jining City during 2024–2025, and to provide scientific evidence for avian influenza prevention and control. Methods: A total of 748 poultry-related environmental samples were collected in March, June, September, and December of 2024–2025. Reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) was used to detect influenza A virus and H5 subtype viral RNA. H5-positive samples were subjected to whole-genome sequencing and analyzed using bioinformatics tools. Results: Among the 748 samples, the positivity rate of influenza A virus was 16.04% (120/748), and that of the H5 subtype was 8.16% (61/748). The H5 positivity rate in 2025 (11.88%) was significantly higher than that in 2024 (5.37%). Higher positivity rates were observed in March and December compared to June and September. Twelve complete H5 genomes were obtained, including nine H5N1 and three H5N6 strains. All HA genes belonged to clade 2.3.4.4b. Key mutations related to antigenic drift, replication and adaptation were detected in multiple viral proteins. Conclusions: The positivity rate of H5 subtype avian influenza viruses in Jining City showed an increasing trend during 2024–2025, with higher prevalence in winter and spring. The circulating strains predominantly belonged to clade 2.3.4.4b. Antigenic drift-associated mutations in the HA protein were identified in some strains, which may affect vaccine matching. Enhanced surveillance of H5 viruses and regular evaluation of antigenic compatibility between vaccine and circulating strains are recommended to mitigate potential risks posed by viral genetic variation. Full article

The H5N1 subtype of highly pathogenic avian influenza (HPAI) poses a major zoonotic threat due to its high fatality rate and capacity for cross species transmission. In early 2025, Argentina detected a novel triple reassortant A(H5N1) virus in Chaco Province, combining Eurasian, North American, and South American lineage segments. Genomic analyses of subsequent outbreaks in Buenos Aires and Entre Ríos confirmed persistence of this reassortant and additional HA substitutions (T204K, P251S) potentially linked to increased mammalian receptor affinity. Although PB2 sequences lacked canonical mammalian-adaptive markers (E627K, Q591K, D701N), all contained I292M, a mutation associated with human adaptation. Phylogenetic analyses revealed distinct genotypes and increasing divergence. These findings indicate ongoing viral evolution and adaptation within Argentina, emphasizing the urgent need for sustained genomic surveillance, timely data sharing, and integrated One Health strategies to mitigate zoonotic and socioeconomic risks associated with H5N1 spread in South America. Full article

H5 subtype avian influenza virus (AIV) can infect both chickens and ducks, leading to substantial economic losses. Nevertheless, certain strains cause silent infections in ducks. In this study, a goose-origin clade 2.3.4.4h H5N6 AIV was isolated, which caused high mortality in mixed-gender white leghorn chickens but no deaths in mixed-gender mallard ducks. After independent serial in vitro passage in duck embryo fibroblasts (DEFs) and in vivo passage in specific-pathogen-free (SPF) ducks, the DEF-passage 10 (P10) virus induced markedly higher mortality rates and viral loads in SPF ducks compared to the DEF-P1 virus and the original parental virus prior to passage. Similarly, the in vivo-passaged P3 and P4 viruses exhibited significantly higher mortality rates than the P1 virus in SPF ducks, with 100% mortality and markedly increased viral titers in the organs. A whole-genome SNP analysis identified seven high-frequency mutations in the M1, NA and NS1 proteins. The NS1-F161L substitution virus exhibited significantly increased mortality rates, viral loads in multiple tissues, and a robustly induced innate immune response in ducks. Furthermore, dynamic evolutionary variations in the NS1 protein among global H5 avian influenza viruses revealed that the NS1-F161L substitution became dominant in clade 2.3.4.4b viruses in 2021 and subsequent years. Collectively, our findings demonstrate that host-driven adaptation can rapidly increase the pathogenicity of H5N6 AIVs in ducks and identify NS1-F161L as a critical virulence marker. These results offer novel insights relevant to the molecular surveillance, virulence prediction, and risk assessment of circulating H5 AIVs in waterfowl. Full article

The ongoing panzootic of the highly pathogenic avian influenza (HPAI) H5N1 virus, dominated by clade 2.3.4.4b, constitutes a significant global threat to wildlife, animal health, and public health. Once characterized by sporadic outbreaks, H5N1 has evolved into a sustained, year-round infection with an expanded host range that now includes numerous mammalian species. Its high pathogenicity is primarily driven by the acquisition of a polybasic haemagglutinin cleavage site, enabling systemic viral spread, alongside emerging endothelial and neurotropic properties that contribute to severe disease and high mortality in mammals. Although zoonotic transmission remains limited, H5N1 continues to accumulate mutations associated with mammalian adaptation, particularly within the haemagglutinin and polymerase complex. Notably, recent outbreaks in U.S. dairy cattle highlight the emergence of novel mammalian reservoirs with increased human exposure risk. Concurrently, vaccination strategies are advancing beyond traditional adjuvanted inactivated vaccines toward next-generation platforms, including mRNA and virus-like particle vaccines, designed for rapid deployment and broader immune protection. However, ongoing viral evolution, constrained vaccine availability, and gaps in coordinated surveillance underscore the urgent need for an integrated One Health approach to reduce panzootic risk. Full article

The review deals with the current knowledge on the global panzootic spread of highly pathogenic avian influenza viruses (HPAIVs), with an emphasis on the H5N1 clade 2.3.4.4b virus. It describes the viral structure, replication, pathotypes and molecular determinants of host range, including sialic-acid receptor usage and key genetic mammalian-adaptation markers (PB2-E627K and PB2-D701N mutations). The host spectrum nowadays extends from wild waterfowl and poultry including seabirds, terrestrial and marine mammals and, based largely on experimental studies or molecular detection, reptiles, amphibians, and fish. Recently, the H5N1 clade 2.3.4.4b virus has shown marked tropism for lactating mammary epithelium in dairy cattle, with virions shed in raw milk. The review reports epidemiology, geographical expansion, clinical presentation, pathogenesis and pathology, diagnosis, immune responses and vaccination approaches across species. It also analyses European Union (EU) and Italian regulatory frameworks, surveillance strategies and biosecurity measures from a One-Health perspective. The review highlights how climate change, wildlife–livestock interfaces, intensive farming and global trade favor viral persistence and genomic reassortment and concludes by stressing strategic actions to limit further host adaptation and panzootic/pandemic risks. Full article

Avian influenza viruses (AIVs), including H5N1 and H7N9, from the Orthomyxoviridae family present substantial public health concerns. The predominant circulating clade 2.3.4.4b has demonstrated enhanced capacity for mammalian adaptation, raising concerns about potential reassortment with human seasonal influenza viruses. Unlike H7N9’s limited host range, H5N1 infects birds, various mammals, and humans. Recent concerns include widespread H5N1 infection of U.S. dairy cattle across 18 states, affecting over 1000 herds with 71 human infections (70 H5N1 and 1 H5N5). Key observations include cow-to-cow transmission, viral presence in milk, and transmission to humans, mainly through occupational exposure. Evidence of mammal-to-mammal transmission has been documented in European and Canadian foxes and South American marine mammals. Standard pasteurization effectively inactivates the virus in milk. The continuing mammalian adaptations, particularly mutations like PB2-E627K, PB2-D701N, and PB2-M535I, suggest potential for further evolution in new hosts, emphasizing the need for enhanced surveillance to mitigate pandemic risks. Full article

Highly pathogenic avian influenza (HPAI) A(H5N1) clade 2.3.4.4b has recently emerged as a major threat to wildlife, agriculture, and public health due to its expanding host range and the increasing frequency of spillover into mammals. In July–August 2023, the mass death of over 3500 northern fur seals (Callorhinus ursinus) and at least one Steller sea lion (Eumetopias jubatus) was recorded on Tyuleniy Island in the Sea of Okhotsk, Russia. Two HPAI A(H5N1) viruses were isolated from fur seal carcasses and designated A/Northern_fur_seal/Russia_Tyuleniy/74/2023 and A/Northern_fur_seal/Russia_Tyuleniy/75/2023. Both viruses exhibited high pathogenicity in chickens (IVPI 2.7–3.0) and mice (MLD₅₀ 1.9–2.5 log₁₀EID₅₀/mL), with distinct differences in disease progression, histopathology, and organ tropism. Experimental infection of mice revealed that strain A/74/2023 induced more severe pulmonary and neurological lesions than A/75/2023. Whole-genome sequencing and phylogenetic analysis demonstrated close relatedness to HPAI H5N1 strains circulating in the Russian Far East and Japan from 2022 to 2023, with several mutations associated with mammalian adaptation, including NP-N319K and, in one isolate, PB2-E627K. According to our findings, northern fur seals (Callorhinus ursinus) on Tyuleniy Island acted as spillover hosts for the highly pathogenic avian influenza (HPAI) H5N1 virus of clade 2.3.4.4b. Furthermore, the high population density of fur seals and the extensive mortality observed during the outbreak highlight these animals’ potential role as another vessel for the evolution of avian influenza viruses. This study represents the first documented case of HPAI H5N1 in pinnipeds in the North Pacific region and supports previous reports indicating that pinnipeds, including northern fur seals, are highly susceptible to HPAI H5N1 clade 2.3.4.4b viruses. Full article

To investigate the molecular characteristics of H3N2 canine influenza viruses circulating in Jiangsu, China, we isolated a H3N2 strain (A/Canine/Nanjing/CnNj01-2025) from a dog presenting with respiratory signs at the Veterinary Teaching Hospital of Nanjing Agricultural University. All eight gene segments were sequenced and compared with those of two human H3N2 strains and five avian H3N2 strains. Antigenicity and receptor-binding properties were also assessed. Phylogenetic analysis revealed that the canine isolate descended from the avian lineage and formed an independent evolutionary clade, while the human strains were more distantly related to the avian lineage. Glycosylation analysis of the HA protein revealed that the canine strain carried seven N-glycosylation sites, including a unique site at residue 97/81 (HA/H3 numbering), which serves as a molecular signature of the canine strain. Several amino-acid substitutions were identified in major antigenic sites, including D97/81N, A176/160T, N204/188D, V212/196I, and W237/222L. Analysis of internal genes showed that the canine strain harbored PB2 292T and 590S mammalian adaptation mutations, which are also present in human strains. Hemagglutination inhibition (HI) assays of the canine strain indicated moderate serologic cross-reactivity with a human H3N2 antiserum (16-fold reduction), whereas avian strains showed no cross-reactivity. Receptor-binding assays demonstrated that the virus retained predominant α-2,3 sialic acid binding, comparable to that of avian influenza viruses, and gained a modest affinity for human-type α-2,6 sialic acid receptors. Therefore, the canine H3N2 virus has undergone significant antigenic drift, developed partial serological cross-reactivity with human strains, and acquired detectable but limited binding affinity for human-type receptors. Overall, our findings suggest that the current canine H3N2 influenza virus exhibits distinct genetic and antigenic variations from human and avian strains. Continuous molecular and serological surveillance of canine influenza viruses is therefore warranted to monitor their evolutionary trends and assess the potential for cross-species transmission. Full article

Highly Pathogenic Avian Influenza (HPAI) viruses, particularly IAV (H5N1), continue to pose a major global threat due to their widespread circulation and high mortality rates in birds. Management of HPAI is complicated by challenges in conserving migratory bird populations, sustaining poultry production, and uncertainties in disease dynamics. Structured decision-making frameworks, such as those based on the PrOACT model, are recommended to improve outbreak response and guide critical actions, especially when HPAI virus (HPAIV) detections occur in sensitive areas like wildlife refuges. Surveillance data from late 2024 to early 2025 show persistent HPAI activity, with 743 detections across 22 European countries and beyond, and notable outbreaks in poultry in nations like Hungary, Iceland, and the UK. The proximity of poultry farms to water sources increases environmental contamination risks. Meanwhile, HPAI A(IAV (H5N1)) and other H5Nx viruses have been detected in a wide range of mammalian species globally, raising concerns about mammalian adaptation due to mutations like E627K and D701N in the PB2 protein. Human infections with IAV (H5N1) have also been reported, with recent cases in North America highlighting zoonotic transmission risks. Molecular studies emphasize the importance of monitoring genetic variations associated with increased virulence and antiviral resistance. Preventive strategies focus on biosafety, personal protective measures, and vaccine development for both avian and human populations. Ongoing genetic characterization and vigilant surveillance remain critical to managing the evolving threat posed by HPAI viruses. Full article

Influenza A virus (IAV) has a wide range of avian and mammalian hosts, leading to disease outbreaks and increasing the risk of panzootics and pandemics. Subtype H5N1 of clade 2.3.4.4b is causing the current high pathogenicity avian influenza (HPAI) panzootic. Environmental changes are fuelling the spread of HPAI H5N1 in wildlife worldwide, with occasional spillover events from seabirds to cetaceans. Sampling difficulties and limited tests available for diagnosis are a challenge to cetacean virology research. Understanding the risk of HPAI outbreaks in cetaceans requires a comprehensive examination of events of IAV infection. Documented cases relate to IAV subtypes H1N3, H13N2, H13N9, and H5N1 and have been reported in cetaceans sampled in the Pacific, Atlantic, and Arctic Oceans. The number of H5N1 IAV isolated from cetaceans is increasing and affects six host species of the families Delphinidae and Phocoenidae of the suborder Odontoceti. The analysis of 40 molecular markers of viral adaptation to mammals in 21 H5N1 cetacean isolates reveals mutations are present in three viral proteins: hemagglutinin (HA), polymerase basic protein 2 (PB2), and nucleoprotein (NP). Phylogenetic analysis of HA and PB2 sequences isolated from cetaceans and co-occurring cases in seabirds and marine mammals do not support sustained transmission of the virus between cetaceans. IAV H5N1 appears to be reaching cetaceans after spillover from seabirds and other marine mammals. Increasing worldwide surveillance of IAV infection of cetaceans is crucial, as these marine mammals are sentinel species for human pandemic preparedness and key species for marine biodiversity conservation and ecosystem health. Full article