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Four types of influenza virus have been identified in nature: influenza A, B, and C viruses are capable of infecting humans, and influenzas A and B cause annual epidemics (seasonal flu) in humans; however, influenza D is currently known to infect only pigs and cattle. The influenza A viruses (IAVs) are of greatest importance to humans, causing widespread significant morbidity and mortality, and have been responsible for at least five pandemics documented since the beginning of the 20th century (Table 1). The H1N1 and H3N2 IAVs continue to circulate in humans as seasonal influenza. In addition to humans, IAVs have a wide range of host animal species in nature, especially wild aquatic birds, the reservoir hosts of IAVs. The IAVs isolated from or adapted to an avian host are named avian influenza viruses (AIVs), and are of great concern owing to their involvement in the genesis of pandemic and outbreak strains. Moreover, the majority of AIVs persist in wild birds and domestic poultry, and novel variants continue to emerge in birds and other hosts, posing non-negligible threats to host ecology and public health. Bi et al. offer a primer on the ecology and transmission of avian influenza viruses and discuss the implications for both human and wildlife health. [ABSTRACT FROM AUTHOR]

Avian coronaviruses (ACoV) have been shown to be highly prevalent in wild bird populations. More work on avian coronavirus detection and diversity estimation is needed for the breeding territories of migrating birds, where the high diversity and high prevalence of Orthomyxoviridae and Paramyxoviridae have already been shown in wild birds. In order to detect ACoV RNA, we conducted PCR diagnostics of cloacal swab samples from birds, which we monitored during avian influenza A virus surveillance activities. Samples from two distant Asian regions of Russia (Sakhalin region and Novosibirsk region) were tested. Amplified fragments of the RNA-dependent RNA-polymerase (RdRp) of positive samples were partially sequenced to determine the species of Coronaviridae represented. The study revealed a high presence of ACoV among wild birds in Russia. Moreover, there was a high presence of birds co-infected with avian coronavirus, avian influenza virus, and avian paramyxovirus. We found one case of triple co-infection in a Northern Pintail (Anas acuta). Phylogenetic analysis revealed the circulation of a Gammacoronavirus species. A Deltacoronavirus species was not detected, which supports the data regarding the low prevalence of deltacoronaviruses among surveyed bird species. [ABSTRACT FROM AUTHOR]

During avian influenza virus surveillance (AIV) carried out in September 2019 in the Lake Baikal basin (Northeast Asia, Russia), one cloacal swab was taken from each of 144 wild birds. The incidence of avian infections caused by viruses of the I Orthomyxoviridae i and I Paramyxoviridae i families appears to be seasonal, with the highest isolation rate being in juvenile birds in the fall of the year (Dorzhiev et al., [3]). Due to its physiographic characteristics, Northeast Asia plays a key role in the abundance, distribution, and migration ecology of wild bird species (Sharshov et al., [19]). [Extracted from the article]

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The genome composition of a given avian influenza virus is the primary determinant of its potential for cross‐species transmission from birds to humans. Here, we introduce a viral genome‐based computational tool that can be used to evaluate the human infectivity of avian isolates of influenza A H7N9 viruses, which can enable prediction of the potential risk of these isolates infecting humans. This tool, which is based on a novel class weight‐biased logistic regression (CWBLR) algorithm, uses the sequences of the eight genome segments of an H7N9 strain as the input and gives the probability of this strain infecting humans (reflecting its human infectivity). We examined the replication efficiency and the pathogenicity of several H7N9 avian isolates that were predicted to have very low or high human infectivity by the CWBLR model in cell culture and in mice, and found that the strains with high predicted human infectivity replicated more efficiently in mammalian cells and were more infective in mice than those that were predicted to have low human infectivity. These results demonstrate that our CWBLR model can serve as a powerful tool for predicting the human infectivity and cross‐species transmission risks of H7N9 avian strains. [ABSTRACT FROM AUTHOR]

We have surveyed avian influenza virus (AIV) genomes from live poultry markets within China since 2014. Here we present a total of 16,091 samples that were collected from May 2016 to February 2019 in 23 provinces and municipalities in China. We identify 2048 AIV-positive samples and perform next generation sequencing. AIV-positive rates (12.73%) from samples had decreased substantially since 2016, compared to that during 2014–2016 (26.90%). Additionally, H9N2 has replaced H5N6 and H7N9 as the dominant AIV subtype in both chickens and ducks. Notably, novel reassortants and variants continually emerged and disseminated in avian populations, including H7N3, H9N9, H9N6 and H5N6 variants. Importantly, almost all of the H9 AIVs and many H7N9 and H6N2 strains prefer human-type receptors, posing an increased risk for human infections. In summary, our nation-wide surveillance highlights substantial changes in the circulation of AIVs since 2016, which greatly impacts the prevention and control of AIVs in China and worldwide. In this study, the authors present a genomic surveillance of avian influenza genomes sampled from live poultry markets in China. They report that a number of variants have emerged since 2016 that pose an increased risk to humans. They highlight the importance of continuous genome surveillance of circulating influenza strains. [ABSTRACT FROM AUTHOR]

H3N2 canine influenza virus (CIV) originated from avian species and emerged in dogs in Asia around 2005 where it became enzootic before reaching the USA in 2015. To investigate the key aspects of the evolution of H3N2 CIV regarding its emergence and adaptation in the canine host, we conducted an extensive analysis of all publicly available H3N2 CIV sequences spanning a 10‐year period. We believe that H3N2 AIVs transferred to canines around 2002–2004. Furthermore, H3N2 CIVs could be divided into seven major clades with strong geographic clustering and some changed sites evidence of adaptive evolution. Most notably, the dN/dS of each H3N2 CIVs segment was higher than the correspondent of H3N2 AIVs and the U content of HA and NA was increasing over time, suggesting the idea that this avian‐origin virus may be gradually adapting to the host. Our results provide a framework to elucidate a general mechanism for emergence of novel influenza viruses. [ABSTRACT FROM AUTHOR]

In May 2016, a highly pathogenic avian influenza A(H5N8) virus strain caused deaths among 3 species of wild migratory birds in Qinghai Lake, China. Genetic analysis showed that the novel reassortant virus belongs to group B H5N8 viruses and that the reassortment events likely occurred in early 2016. [ABSTRACT FROM AUTHOR]

Background:  The emergence of infections by the novel avian influenza A(H7N9) virus has posed a threat to human health. Cross-immunity between A(H7N9) and other heterosubtypic influenza viruses affected by antigenicity-dependent substitutions needs to be investigated.Methods:  We investigated the cellular and humoral immune responses against A(H7N9) and 2009 pandemic influenza A(H1N1) virus (A[H1N1]pdm09), by serological and T-cell-specific assays, in a healthy population. The molecular bases of the cellular and humoral antigenic variability of A(H7N9) were illuminated by structural determination.Results:  We not only found that antibodies against A(H7N9) were lacking in the studied population, but also revealed that both CD4+ and CD8+ T cells that cross-reacted with A(H7N9) were at significantly lower levels than those against the A(H1N1)pdm09 peptides with substitutions. Moreover, individual peptides for A(H7N9) with low cross-reactivity were identified. Structural determination indicated that substitutions within these peptides influence the antigenic variability of A(H7N9) through both major histocompatibility complex (MHC) binding and T-cell receptor docking.Conclusions:  The impact of antigenicity-dependent substitutions on cross-reactivity of T-cell immunity against the novel influenza virus A(H7N9) in the healthy population benefits the understanding of immune evasion of influenza viruses and provides a useful reference for universal vaccine development. [ABSTRACT FROM AUTHOR]

The receptor-binding specificity of influenza A viruses is a major determinant for the host tropism of the virus, which enables interspecies transmission. In 2013, the first human case of infection with avian influenza A (H6N1) virus was reported in Taiwan. To gather evidence concerning the epidemic potential of H6 subtype viruses, we performed comprehensive analysis of receptor-binding properties of Taiwan-isolated H6 HAs from 1972 to 2013. We propose that the receptor-binding properties of Taiwan-isolated H6 HAs have undergone three major stages: initially avian receptor-binding preference, secondarily obtaining human receptor-binding capacity, and recently human receptor-binding preference, which has been confirmed by receptor-binding assessment of three representative virus isolates. Mutagenesis work revealed that E190V and G228S substitutions are important to acquire the human receptor-binding capacity, and the P186L substitution could reduce the binding to avian receptor. Further structural analysis revealed how the P186L substitution in the receptor-binding site of HA determines the receptor-binding preference change. We conclude that the human-infecting H6N1 evolved into a human receptor preference. [ABSTRACT FROM AUTHOR]

Approximately 100 migratory birds, including whooper swans and pochards, were found dead in the Sanmenxia Reservoir Area of China during January 2015. The causative agent behind this outbreak was identified as H5N1 highly pathogenic avian influenza virus (HPAIV). Genetic and phylogenetic analyses revealed that this Sanmenxia H5N1 virus was a novel reassortant, possessing a Clade 2.3.2.1c HA gene and a H9N2-derived PB2 gene. Sanmenxia Clade 2.3.2.1c-like H5N1 viruses possess the closest genetic identity to A/Alberta/01/2014 (H5N1), which recently caused a fatal respiratory infection in Canada with signs of meningoencephalitis, a highly unusual symptom with influenza infections in humans. Furthermore, this virus was shown to be highly pathogenic to both birds and mammals, and demonstrate tropism for the nervous system. Due to the geographical location of Sanmenxia, these novel H5N1 viruses also have the potential to be imported to other regions through the migration of wild birds, similar to the H5N1 outbreak amongst migratory birds in Qinghai Lake during 2005. Therefore, further investigation and monitoring is required to prevent this novel reassortant virus from becoming a new threat to public health. [ABSTRACT FROM AUTHOR]

[Display omitted] Migratory birds are considered natural reservoirs of avian influenza A viruses (AIVs). To further our viral ecology knowledge and understand the subsequent risk posed by wild birds, we conducted a 4-year surveillance study of AIVs in the bird wintering wetlands of the Yangtze River, China. We collected over 8000 samples and isolated 122 AIV strains. Analyses were then carried out with 108 novel sequenced genomes and data were deposited in GISAID and other public databases. The results showed that the Yangtze River wintering wetlands functioned as a mixing ground, where various subtypes of AIVs were detected harboring a high diversity of nucleotide sequences; moreover, a portion of AIV gene segments were persistent inter-seasonally. Phylogenetic incongruence presented complex reassortment events and distinct patterns among various subtypes. In addition, we observed that viral gene segments in wintering wetlands were closely related to known North American isolates, indicating that intercontinental gene flow occurred. Notably, highly pathogenic H5 and low pathogenic H9 viruses, which usually circulate in poultry, were found to have crossed the poultry/wild bird interface, with the viruses introduced to wintering birds. Overall, this study represented the largest AIV surveillance effort of wild birds within the Yangtze River wintering wetlands. Surveillance data highlighted the important role of wintering wild birds in the ecology of AIVs and may enable future early warnings of novel AIV emergence. [ABSTRACT FROM AUTHOR]

Highlights • A recombinant genotype VII NDV co-expressing H9 subtype hemagglutinin was developed. • Insertion of the chimeric HA-F resulted in a recombinant virus with enhanced HA protein incorporation into virions. • rmNA-H9F induces both systemic and local immunity, providing full protection against NDV and AIV challenge. Abstract Newcastle disease virus (NDV) and H9 subtype avian influenza virus (AIV) are two avian pathogens across the globe. Inasmuch as most poultry flocks worldwide are vaccinated with a live low-virulence or attenuated NDV vaccine, we embarked on the development of vaccine prototypes that would have dual specificities and would allow a single immunization against both avian influenza (AI) and Newcastle disease (ND). Therefore, in the present work, a cloned full-length copy of the genome of the lentogenic NDV strain rmNA-1 was selected as a backbone vector to construct three chimeric NDVs that expressed (i) the ORF encoding the HA, (ii) the ectodomain of HA fused with the transmembrane domain and cytoplasmic tail regions derived from the NDV F protein and (iii) the ectodomain of HA fused with a short GS linker and the GCN4 sequences, and designated as rmNA-H9, rmNA-H9F, and rmNA-H9 (ECTO), respectively. rmNA-H9, rmNA-H9F, and rmNA-H9 (ECTO) stably expressed the modified HA gene for 10 egg passages and the three recombinants were found innocuous to chickens. The insertion of the chimeric HA-F, rather than HA-ECTO or ORF of HA, resulted in a recombinant virus with enhanced incorporation of the HA protein into the viral surface. A single immunization of SPF chickens with the three recombinants induced NDV- and AIV H9-specific antibodies, and protected chickens against a challenge with a lethal dose of velogenic NDV or AIV H9N2. Remarkably, non-shedding of influenza virus and higher levels of H9 subtype HI titers were observed 7 days post challenge (dpc) in rmNA-H9F vaccinated chickens, than other recombinants. Furthermore, a prime-boost vaccination of chickens with rmNA-H9F induced higher levels of NDV- and H9- HI and secretory IgA, as well as reduced viral shedding and virus-induced gross lesions, compared with the commercial vaccine. Therefore, the recombinant rmNA-H9F is a promising bivalent vaccine candidate against NDV and H9 subtype AIV in chickens. [ABSTRACT FROM AUTHOR]

• Reassortant 2.3.4.4b H5N8 HPAIVs were isolated from the live poultry market in Xinjiang, China. • The viral gene segments of the isolates were from multiple geographic origins. • The isolates could transmit into Xinjiang by migratory birds. • Multiple mutations in the viral proteins were associated with changes in pathogenicity. • The wetlands of Northern Tianshan Mountain may play a key role in AIVs dissemination. In 2016, H5N8 avian influenza viruses of clade 2.3.4.4b were detected at Qinghai Lake, China. Afterwards, the viruses of this clade rapidly spread to Asia, Europe, and Africa via migratory birds, and caused massive deaths in poultry and wild birds globally. In this study, four H5N8 isolates (abbreviated as 001, 002, 003, and 004) were isolated from the live poultry market in Xinjiang in 2017. Phylogenetic analysis showed that the hemagglutinin genes of the four isolates belonged to clade 2.3.4.4b, while the viral gene segments were from multiple geographic origins. For 002, the polymerase acidic gene had the highest sequence homology (99.55 %) with H5N8 virus identified from green-winged teal in Egypt in 2016, and the remaining genes exhibited the highest sequence homologies (99.18–100 %) with those of H5N8 viruses isolated from domestic duck sampled in Siberia in 2016. The polymerase basic 1 gene clustered together with H5N8 virus identified from painted stork of India in 2016, and the remaining genes had relatively close genetic relationships with H5N8 viruses identified from the duck of Siberia in 2016 and turkey in Italy in 2017. For the other three isolates, the nucleoprotein gene of 001 had the highest sequence homology (98.82 %) and relatively close genetic relationship with H9N2 viruses identified from poultry in Vietnam and Cambodia in 2015–2017, and all the remaining genes had the highest sequence homologies (99.18 %–99.58 %) and relatively close genetic relationships with H5N8 viruses identified from poultry and waterfowl sampled in African countries in 2017 and swan sampled in China in 2016. Multiple basic amino acids were observed at cleavage sites in the hemagglutinin proteins of the H5N8 isolates, indicating high pathogenicity. In addition, the L89V, G309D, R477G, I495V, A676T and I504V mutations in the polymerase basic 2 protein, N30D and T215A mutations in the matrix 1 protein, P42S mutation, and 80−84 amino acid deletion in the nonstructural 1 protein were detected in all isolates. These mutations were associated with increased virulence and polymerase activity in mammals. Therefore, our results indicate that the H5N8 isolates involved multiple introductions of reassorted viruses, and also revealed that the wetlands of Northern Tianshan Mountain may play a key role in H5N8 AIVs disseminating among Central China, the Eurasian continent, and East African Countries. [ABSTRACT FROM AUTHOR]