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In early 2013, human infections caused by a novel H7N9 avian influenza virus (AIV) were first reported in China; these infections caused severe disease and death. The virus was initially low pathogenic to poultry, enabling it to spread widely in different provinces, especially in live poultry markets. Importantly, the H7N9 low pathogenic AIVs (LPAIVs) evolved into highly pathogenic AIVs (HPAIVs) in the beginning of 2017, causing a greater threat to human health and devastating losses to the poultry industry. Fortunately, nationwide vaccination of chickens with an H5/H7 bivalent inactivated avian influenza vaccine since September 2017 has successfully controlled H7N9 avian influenza infections in poultry and, importantly, has also prevented human infections. In this review, we summarize the biological properties of the H7N9 viruses, specifically their genetic evolution, adaptation, pathogenesis, receptor binding, transmission, drug resistance, and antigenic variation, as well as the prevention and control measures. The information obtained from investigating and managing the H7N9 viruses could improve our ability to understand other novel AIVs and formulate effective measures to control their threat to humans and animals.

Many parasites induce decreased host movement, known as lethargy, which can impact disease spread and the evolution of virulence. Mathematical models have investigated virulence evolution when parasites cause host death, but disease-induced decreased host movement has received relatively less attention. Here, we consider a model where, due to the within-host parasite replication rate, an infected host can become lethargic and shift from a moving to a resting state, where it can die. We find that when the lethargy and disease-induced mortality costs to the parasites are not high, then evolutionary bistability can arise, and either moderate or high virulence can evolve depending on the initial virulence and the magnitude of mutation. These results suggest, firstly, the transient coexistence of strains with different virulence, which may explain the coexistence of low- and high-pathogenic strains of avian influenza and human immunodeficiency viruses, and secondly, that medical interventions to treat the symptoms of lethargy or prevent disease-induced host deaths can result in a large jump in virulence and the rapid evolution of high virulence. In complement to existing results that show bistability when hosts are heterogeneous at the population-level, we show that evolutionary bistability may arise due to transmission heterogeneity at the individual host-level.

Influenza is a global challenge, and future pandemics of influenza are inevitable. One of the lessons learned from past pandemics is that all pandemic influenza viruses characterized to date possess viral genes originating from avian influenza viruses (AIVs). During the past decades, a wide range of AIVs have overcome the species barrier and infected humans with different clinical manifestations ranging from mild illness to severe disease and even death. Understanding the mechanisms of infection in the context of clinical outcomes, the mechanism of interspecies transmission, and the molecular determinants that confer interspecies transmission is important for pandemic preparedness. Here, we summarize the epidemiology, virology, and pathogenicity of human infections with AIVs to further our understanding of interspecies transmission.

Objective: The highly pathogenic avian influenza virus (HPAIV) is a threat to the poultry industry as well as the economy and remains a potential source of pandemic infection in humans. Antiviral genes are considered a potential factor for HPAIV resistance. Therefore, in this study, we investigated gene expression related to cytokine-cytokine receptor interactions by comparing resistant and susceptible Ri chicken lines for avian influenza virus infection.Methods: Ri chickens of resistant (Mx/A; BF2/B21) and susceptible (Mx/G; BF2/B13) lines were selected by genotyping the Mx dynamin like GTPase (Mx) and major histocompatibility complex class I antigen BF2 genes. These chickens were then infected with influenza A virus subtype H5N1, and their lung tissues were collected for RNA sequencing.Results: In total, 972 differentially expressed genes (DEGs) were observed between resistant and susceptible Ri chickens, according to the gene ontology and Kyoto encyclopedia of genes and genomes pathways. In particular, DEGs associated with cytokine-cytokine receptor interactions were most abundant. The expression levels of cytokines (interleukin-1β [IL-1β], IL-6, IL-8, and IL-18), chemokines (C-C Motif chemokine ligand 4 [CCL4] and CCL17), interferons (IFN-γ), and IFN-stimulated genes (Mx1, CCL19, 2’-5’-oligoadenylate synthaselike, and protein kinase R) were higher in H5N1-resistant chickens than in H5N1-susceptible chickens.Conclusion: Resistant chickens show stronger immune responses and antiviral activity (cytokines, chemokines, and IFN-stimulated genes) than those of susceptible chickens against HPAIV infection.

The appearance in the XXI century the respiratory tract viral infections, which acquired emergent signs (of SARS, influenza A (H5N1, H1N1), MERS-CoV) cause a rather high mortality rate. The unpredictability of the influenza viruses evolution cause concern among experts around the world. Goal. To conduct a comparative analysis of the clinical and laboratory features with influenza A (H1N1) in adults with the development of complications, as well as the evaluation of the assigned initial therapy with pneumonia. Materials and methods. We examined and treated 472 cases of influenza, in 72 patients of them were radiologically confirmed pneumonia, 69 of them were hospitalized in the intensive care unit (ICU) of KMKL № 4. We analyzed clinical and laboratory picture flu in adults caused by influenza A virus (H1N1). Results and discussion. Pneumonia - one of the most frequent complications of influenza, which significantly affects the prognosis. Results: unfavorable prognostic criteria are: later seeking medical help (5 - 6 day of illness), the development of acute respiratory distress syndrome (ARDS), increased white blood cell count and the presence of severe comorbidity. Conclusions. The results of the analysis of comorbidity of different systems and organs 21 Здоров’я суспільства № 3-4 – 2016 / Здоровье общества № 3-4 – 2016 / The Health of Society № 3-4 – 2016 in patients with influenza A (H1N1) show that cardiovascular diseases, endocrine system and the blood is a risk factor not only serious current, but also fatal disease at a young age. The prognosis and severity significantly influences - Early assignment of causal treatment and the Nukleksu in recommended doses appointment significantly reduce the development of other complications and cut the length of patients' residence in hospital.

Le concept « une seule santé » lie étroitement la santé humaine et la santé animale car de nombreuses maladies sont des zoonoses. Les exemples historiques témoignant d’une collaboration efficace entre la médecine vétérinaire et la médecine humaine sont nombreux dans la mise au point des premiers vaccins utilisés dans le monde (variole, rage, tétanos, diphtérie, tuberculose, etc.). Mais lorsqu’une maladie nouvelle apparaît chez l’animal, le risque d’une transmission possible à l’Homme est difficile à estimer. Dans ce dernier cas, la perte de confiance du consommateur face aux incertitudes scientifiques peut provoquer une crise sanitaire (exemples de l’encéphalopathie spongiforme bovine et de la peste aviaire H5N1). Mais la plus grave crise que nous connaissons depuis le début de l’année 2020 est celle de la pandémie de Covid-19 qui confirme que la modification des écosystèmes de certaines espèces sauvages comme la chauve-souris fer à cheval peut avoir des conséquences importantes pour la santé publique. Les animaux ayant été malades de la Covid-19 ont été contaminés par l’Homme mais on ne peut pas exclure actuellement le risque de réservoir animal pour le SARS-CoV-2 qui a circulé dans le monde entier.

A growing body of evidence suggests the pivotal role of long non-coding RNA (lncRNA) in influenza virus infection. Based on next-generation sequencing, we previously demonstrated that Lnc45 was distinctively stimulated by H5N1 influenza virus in mice. In this study, we systematically investigated the specific role of Lnc45 during influenza A virus (IAV) infection. Through qRT-PCR, we first demonstrated that Lnc45 is highly up-regulated by different subtypes of IAV strains, including H5N1, H7N9, and H1N1 viruses. Using RNA-FISH and qRT-PCR, we then found that Lnc45 can translocate from nuclear to cytoplasm during H5N1 virus infection. In addition, forced Lnc45 expression dramatically impeded viral replication of H1N1, H5N1, and H7N9 virus, while abolish of Lnc45 expression by RNA interference favored replication of these viruses, highlighting the potential broad antiviral activity of Lnc45 to IAV. Correspondingly, overexpression of Lnc45 inhibited viral polymerase activity and suppressed IAV-induced cell apoptosis. Moreover, Lnc45 significantly restrained nuclear aggregation of viral NP and PA proteins during H5N1 virus infection. Further functional study revealed that the stem ring arms of Lnc45 mainly mediated the antiviral effect. Therefore, we here demonstrated that Lnc45 functions as a broad-spectrum antiviral factor to inhibit influenza virus replication probably through inhibiting polymerase activity and NP and PA nuclear accumulation via its stem ring arms. Our study not only advances our understanding of the complexity of the IAV pathogenesis but also lays the foundation for developing novel anti-IAV therapeutics targeting the host lncRNA.

To date, only low pathogenic (LP) H5 and H7 avian influenza viruses (AIV) have been observed to naturally shift to a highly pathogenic (HP) phenotype after mutation of the monobasic hemagglutinin (HA) cleavage site (HACS) to polybasic motifs. The LPAIV monobasic HACS is activated by tissue-restricted trypsin-like enzymes, while the HPAIV polybasic HACS is activated by ubiquitous furin-like enzymes. However, glycosylation near the HACS can affect proteolytic activation and reduced virulence of some HPAIV in chickens. In 2012, a unique H4N2 virus with a polybasic HACS was isolated from quails but was LP in chickens. Whether glycosylation sites (GS) near the HACS hinder the evolution of HPAIV H4N2 remains unclear. Here, we analyzed the prevalence of potential GS in the N-terminus of HA1, 2NYT4 and 18NGT20, in all AIV sequences and studied their impact on H4N2 virus fitness. Although the two motifs are conserved, some non-H5/H7 subtypes lack one or both GS. Both sites were glycosylated in this H4N2 virus. Deglycosylation increased trypsin-independent replication in cell culture, cell-to-cell spread and syncytium formation at low-acidic pH, but negatively affected the thermostability and receptor-binding affinity. Alteration of 2NYT4 with or without 18NGT20 enabled systemic spread of the virus to different organs including the brain of chicken embryos. However, all intranasally inoculated chickens did not show clinical signs. Together, although the conserved GS near the HACS are important for HA stability and receptor binding, deglycosylation increased the H4N2 HA-activation, replication and tissue tropism suggesting a potential role for virus adaptation in poultry.

Low pathogenic avian influenza viruses (LPAIVs) have been widespread in poultry and wild birds throughout the world for many decades. LPAIV infections are usually asymptomatic or cause subclinical symptoms. However, the genetic reassortment of LPAIVs may generate novel viruses with increased virulence and cross-species transmission, posing potential risks to public health. To evaluate the epidemic potential and infection landscape of LPAIVs in Guangxi Province, China, we collected and analyzed throat and cloacal swab samples from chickens, ducks and geese from the live poultry markets on a regular basis from 2016 to 2019. Among the 7,567 samples, 974 (12.87%) were LPAIVs-positive, with 890 single and 84 mixed infections. Higher yearly isolation rates were observed in 2017 and 2018. Additionally, geese had the highest isolation rate, followed by ducks and chickens. Seasonally, spring had the highest isolation rate. Subtype H3, H4, H6 and H9 viruses were detected over prolonged periods, while H1 and H11 viruses were detected transiently. The predominant subtypes in chickens, ducks and geese were H9, H3, and H6, respectively. The 84 mixed infection samples contained 22 combinations. Most mixed infections involved two subtypes, with H3 + H4 as the most common combination. Our study provides important epidemiological data regarding the isolation rates, distributions of prevalent subtypes and mixed infections of LPAIVs. These results will improve our knowledge and ability to control epidemics, guide disease management strategies and provide early awareness of newly emerged AIV reassortants with pandemic potential.

Zoonoses have a different impact on public health, determined by geographical and socio-economic factors, which requires their prioritization for prevention and control purposes to be performed at the national level. Prioritization of zoonoses is a mechanism used in policy-making, primarily in allocating available resources. Aim of the paper is to compare two different methods used for prioritization of zoonoses by Institute of public health (IPH) and Food and Veterinary Agency (FVA). Material and methods: IPH used a method prepared by the U.S. Centers for Disease Control and Prevention (CDC), - One Health Zoonotic Disease Prioritization (OHZDP) tool, adapted to national conditions (2019). FVA used a standardized semi-quantitative method based on the OIE Methodological Manual (List and Categorization of priority diseases in animals including and those transmitted to humans). A total of 21 zoonoses have been selected, based on their importance for the human and veterinary sector. These diseases are ranked according to the stated criteria of the two previously conducted prioritizations and their comparison is performed. Results: With the prioritization conducted by IPH and FVA the first 5 ranked zoonoses are: Hemorrhagic fevers with renal syndrome, Leishmaniasis, Tularemia, Brucellosis and Listeriosis. With the prioritization carried out by the FVA the first 5 ranked zoonoses are: Bovine brucellosis, Bovine tuberculosis, Salmonellosis, Avian influenza and West Nile fever. A Cumulative Annual Incidence is taken as a control parameter. Regarding this, the 5 first ranked zoonoses are Echinococcosis, Brucellosis, Lyme fever, Leishmaniasis and Tularemia. Conclusions: A comparative analysis of the separate lists of priorities for human and veterinary medicine shows that only a certain percentage overlap. Also, the presence of a number of zoonoses with endemic character, but also a more pronounced risk of new emergent diseases, determines the need to provide consensus on the methodology of prioritization of zoonoses, and its formalization and institutionalization, as a crucial step towards identification and prioritization of zoonoses that would be the subject of joint programs and interventions., Зоонозите имаат различен импакт на јавното здравство, детерминирано од географските и социо-економските фактори, што условува нивната приоритизација за цели на превентива и контрола да биде изведена на национално ниво. Целта на трудот е да се споредат два различни методи што се користат за приоритизирање на зоонозите од Институтот за јавно здравје (ИЈЗ) и Агенцијата за храна и ветеринарство (АХВ). Материјал и методи: ИЈЗ користеше метод подготвен од U.S. Centers for Disease Control and Prevention (CDC), - One Health Zoonotic Disease Prioritization (OHZDP) tool, прилагодена на националните услови (2019). АХВ користеше стандардизиран полу-квантитативен метод заснован на методолошкиот прирачник на OIE (List and Categorization of priority diseases in animals including and those transmitted to humans). Селектирани се вкупно 21 зоонози, врз основа на нивната важност за хумaниот и ветеринарниот сектор. Овие зоонози се рангирани според наведените критериуми на двете претходно спроведени приоритизации и е извршена нивна споредба. Резултати Со приоритизација спроведена од ИЈЗ и АХВ (семи-квантитативна метода Rist CDC), први 5 рангирани зоонози се: Хеморагични трески со бубрежен синдром, Лајшманијаза, Туларемија, Бруцелоза и Листериоза. Со приоритизација спроведена од АХВ (модификација на квантитативниот методот на OIE), први 5 рангирани зоонози се: бруцелоза кај говеда, туберкулоза кај говеда, салмонелоза, авијарна инфлуенза и западнонилска треска. Како контролен параметар е земен кумулативна годишна инциденца (КГИ). Првите 5 рангирани зоонози согласно КГИ се: Ехинококоза, Бруцелоза, Лајмска треска, Лајшманијаза и Туларемија. Заклучоци: Споредбената анализа на одделните листи на приоритетни зоонози за хумана и ветеринарна медицина покажува дека само одредени зоонози се преклопуваат. Исто така, присуството на голем број зоонози со ендемичен карактер, но и поизразен ризик од појава на нови заболувања, ја одредува потребата да се обезбеди консензус за методологијата на приоритизација на зоонози, како и нејзина формализирање и институционализација, како клучен чекор кон идентификување и приоритизирање на зоонози кои би биле предмет на заеднички програми и интервенции.

Elucidation of the molecular pathogenesis underlying virus-host interactions is important for the development of new diagnostic and therapeutic strategies against highly pathogenic avian influenza (HPAI) virus infection in chickens. However, the pathogenesis of HPAI virus in chickens is not completely understood. To identify the intracellular signaling pathways and critical host proteins associated with influenza pathogenesis, we analyzed the lung proteome of a chicken infected with HPAI H5N1 virus (A/duck/India/02CA10/2011/Agartala). Mass spectrometry data sets were searched against the chicken UniProt reference database. At the local false discovery rate level of 5%, a total of 3313 proteins with the presence of at least one unique peptide were identified in the chicken lung proteome datasets. Differential expression analysis of these proteins showed that 247 and 1754 proteins were downregulated at 12 h and 48 h postinfection, respectively. We observed expression of proteins of the predominant signaling pathways, including Toll-like receptors (TLRs), retinoic acid-inducible gene I-like receptors (RLRs), NOD-like receptors (NLRs), and JAK-STAT signaling. Activation of these pathways is associated with the cytokine storm effect and thus may be the cause of the severity of HPAI H5N1 infection in chickens. We also observed the expression of myeloid differentiation primary response protein (MyD88), inhibitor of nuclear factor kappa B kinase subunit beta (IKBKB), interleukin 1 receptor associated kinase 4 (IRAK4), RELA proto-oncogene NF-κB subunit (RELA), and mitochondrial antiviral signaling protein (MAVS), which are involved in critical signaling pathways, as well as other, less-commonly identified proteins such as hepatocyte nuclear factor 4 alpha (HNF4A), ELAV-like RNA binding protein 1 (ELAVL1), fibronectin 1 (FN1), COP9 signalosome subunit 5 (COPS5), cullin 1 (CUL1), breast cancer type 1 susceptibility protein (BRCA1), and the FYN proto-oncogene Src family tyrosine kinase (FYN) as main hub proteins that might play important roles in influenza pathogenesis in chickens. In summary, we identified the signaling pathways and the proteomic determinants associated with disease pathogenesis in chickens infected with HPAI H5N1 virus.

Outbreaks of avian influenza spread across political boundaries, and migratory birds are often scapegoated as vectors for the disease. This paper develops the vice of biosecurity to explain the ten...

Highly pathogenic avian influenza H5N1 viruses have become endemic in global poultry populations over the past 25 years and pose an ongoing public health threat. Although the incidence of human cases has declined, viruses from the H5N1 lineage can now be found in poultry throughout Asia, the Middle East and Africa, in addition to causing outbreaks in Europe and the Americas. The recent emergence and spread of reassortant H5Nx viruses, resulting in regional poultry outbreaks, has increased the risk for further evolution of these viruses and possible avian-to-human transmission. Ongoing surveillance and pandemic preparedness for H5N1 and other avian influenza viruses of public health concern are warranted.

Prevention of emerging infections in children is a dynamic arena where substantial medical advances have enabled intervention and prevention of infection outbreaks. This article discusses 5 infections causing significant morbidity and mortality across Asia, Latin America, and Africa. Avian influenza and the Middle East respiratory syndrome are highly contagious zoonoses spread through aerosol and droplets, affecting predominantly Asia. Dengue infection and chikungunya are endemic mosquito-borne viruses in tropical regions across Asia, Latin America, and Africa. Ebola is a highly contagious virus spread through human-to-human contact. The latest information in clinical manifestations, infection, prevention control, chemoprophylaxis, vaccination, and public health measures is reviewed.

The paper presents results of avian influenza epidemiological monitoring in the Republic of Crimea in 2019–2020. The attention was focused on the study of water basins of the Azov and Black Seas, the Sivash Lagoon and freshwater lakes in the Feodosia Urban Okrug, Leninsky, Sovetsky, Nizhnegorsky, Chernomorsky and Saksky Raions to detect the avian influenza virus circulation. Examination of the above mentioned areas showed that some freshwater reservoirs became shallow and dry, and aquatic vegetation degraded. The natural biotope analysis conducted in 2019 and 2020 showed a decreased number of semiaquatic wild birds. The pathological material was sampled from semiaquatic and migratory wild birds, as well as from poultry kept in poultry farms and backyards. The collected samples were tested using real-time RT-PCR. In 2019, the AIV type A (H9) genome was detected in one fecal sample taken from wild birds near Kuchuk-Adzhigol Lake in Feodosia Urban Okrug. The AIV type A (H5) genome was detected in 2020 during laboratory testing of pathological material taken from the remains of a mute swan within the shoreline of a freshwater lake near the Ermakovo settlement of the Dzhankoysky Raion. The genetic analysis was performed in the FGBI “ARRIAH” (Vladimir), and the N8 subtype neuraminidase of the influenza virus isolate was determined. The comparative genetic analysis of 258 bp nucleic acid sequences of the AIV H gene fragment showed that the identified isolate belongs to the Asian genetic lineage of highly pathogenic AIV subtype H5 (clade 2.3.4.4) associated with the epidemic spread in Asia, Europe, the Middle East and Africa in 2016–2020.

The development of visual tools for the timely identification of spatio-temporal clusters will assist in implementing control measures to prevent further damage. From January 2015 to June 2020, a total number of 1463 avian influenza outbreak farms were detected in Taiwan and further confirmed to be affected by highly pathogenic avian influenza subtype H5Nx. In this study, we adopted two common concepts of spatio-temporal clustering methods, the Knox test and scan statistics, with visual tools to explore the dynamic changes of clustering patterns. Since most (68.6%) of the outbreak farms were detected in 2015, only the data from 2015 was used in this study. The first two-stage algorithm performs the Knox test, which established a threshold of 7 days and identified 11 major clusters in the six counties of southwestern Taiwan, followed by the standard deviational ellipse (SDE) method implemented on each cluster to reveal the transmission direction. The second algorithm applies scan likelihood ratio statistics followed by AGC index to visualize the dynamic changes of the local aggregation pattern of disease clusters at the regional level. Compared to the one-stage aggregation approach, Knox-based and AGC mapping were more sensitive in small-scale spatio-temporal clustering.

In late 2020, we detected 32 highly pathogenic avian influenza A(H5N8) viruses in migratory ducks in Shanghai, China. Phylogenetic analysis of 5 representative isolates identified 2 sublineages of clade 2.3.4.4b. Each sublineage formed separate clusters with isolates from East Asia and Europe.

Avian influenza is a highly dangerous viral disease that causes huge economic damage to poultry farming. Currently, highly virulent influenza virus with N8 neur- aminidase subtype is quite often detected in populations of domestic and wild birds in various countries of the world. The article provides data on complete nucleotide sequences of the neuraminidase gene of highly pathogenic avian influenza virus isolates recovered in the second half of 2020 from pathological material received from four regions of the Russian Federation. The conducted research showed that the subtype of the isolated virus was N8. According to the phylogenetic analysis, isolates of N8 virus belong to group 8C.4. During the phylogenetic analysis of the neuraminidase, we also took into account data on hemagglutinin classification, according to which H5N8 virus isolates belong to a widespread clade 2.3.4.4. Viruses of the clade were first registered in 2010 in China and they have been circulating up to now. The paper also provides data of a comparative analysis of nucleotide sequences of the studied isolates and the isolates from the international GenBank and GISAID databases, recovered in other countries from 2007 to 2020. During the analysis of the amino acid sequence of the studied isolates, no substitutions were found in the positions that affect resistance to neuraminidase inhibitors. The complete nucleotide sequences of the neuraminidase gene of the avian influenza virus subtype N8 (isolates A/domestic goose/OMSK/1521-1/2020, A/duck/Chelyabinsk/1207-1/2020, A/duck/Saratov/1578-2/2020, A/goose/Tatarstan/1730-2/2020) are published in the international GenBank and GISAID databases. Based on the analysis of the nucleotide sequences of the studied isolates, the article shows gradual evolution of the N8 subtype virus.

The highly pathogenic avian influenza H5N6 viruses are widely circulating in poultry and wild birds, and have caused 38 human infections including 21 deaths; however, the key genetic determinants of the pathogenicity of these viruses have yet to be fully investigated. Here, we characterized two H5N6 avian influenza viruses – A/duck/Guangdong/S1330/2016 (GD/330) and A/environment/Fujian/S1160/2016 (FJ/160) – that have similar viral genomes but differ markedly in their lethality in mice. GD/330 is highly pathogenic with a 50% mouse lethal dose (MLD50) of 2.5 log10 50% egg infectious doses (EID50), whereas FJ/160 exhibits low pathogenicity with an MLD50 of 7.4 log10 EID50. We explored the molecular basis for the difference in virulence between these two viruses. By using reverse genetics, we created a series of reassortants and mutants in the GD/330 background and assessed their virulence in mice. We found that the HA gene of FJ/160 substantially attenuated the virulence of GD/330 and that the mutation of glycine (G) to tryptophan (W) at position 225 (H3 numbering) in HA played a key role in this function. We further found that the amino acid mutation G225W in HA decreased the acid and thermal stability and increased the pH of HA activation, thereby attenuating the H5N6 virus in mice. Our study thus identifies a novel molecular determinant in the HA protein and provides a new target for the development of live attenuated vaccines and antiviral drugs against H5 influenza viruses.

Understanding the evolutionary adaptations that enable avian influenza viruses to transmit in mammalian hosts could allow better detection of zoonotic viruses with pandemic potential. We applied ancestral sequence reconstruction to gain viruses representing different adaptive stages of the European avian-like (EA) H1N1 swine influenza virus as it transitioned from avian to swine hosts since 1979. Ancestral viruses representing the avian-like precursor virus and EA swine influenza viruses from 1979–1983, 1984–1987 and 1988–1992 were reconstructed and characterized. Glycan-binding analyses showed stepwise changes in the haemagglutinin receptor–binding specificity of the EA swine influenza viruses—that is, from recognition of both α2,3- and α2,6-linked sialosides to recognition of α2,6-linked sialosides only; however, efficient transmission in piglets was enabled by adaptive changes in the viral polymerase protein and nucleoprotein, which have been fixed since 1983. PB1-Q621R and NP-R351K increased viral replication and transmission in piglets when introduced into the 1979–1983 ancestral virus that lacked efficient transmissibility. The stepwise adaptation of an avian influenza virus to a mammalian host suggests that there may be opportunities to intervene and prevent interspecies jumps through strategic coordination of surveillance and risk assessment activities. Ancestral avian influenza A viruses are used to identify adaptive changes in viral polymerase and nucleoproteins that enable efficient replication and transmission in pigs.

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.

In February 2021, routine sentinel surveillance for influenza-like illness in Cambodia detected a human avian influenza A(H9N2) virus infection. Investigations identified no recent H9N2 virus infections in 43 close contacts. One chicken sample from the infected child's house was positive for H9N2 virus and genetically similar to the human virus.

The ongoing COVID-19 crisis has emphasized more than ever the relevance of wildlife as a potential source of pathogens for other species, including humans, and the potential importance that interactions with wildlife can have on global health. Nevertheless, in the veterinary world, the concept of wildlife as a potential reservoir and source of pathogens detrimental to livestock production and health has been known for centuries. Well-known examples of livestock diseases in which the interface with wildlife plays, or has played, an important role include rinderpest, avian influenza, foot and mouth disease (FMD), and African swine fever (ASF). Rinderpest, caused by a morbillivirus of the family Paramyxoviridae, is one of only two diseases that have been globally eradicated (the other being smallpox in humans), after having caused major disease outbreaks in domestic and wild artiodactyl species for centuries. After a globally coordinated eradication campaign, the World Organisation for Animal Health (OIE) and the Food and Agriculture Organization (FAO) of the United Nations announced in 2011 that rinderpest virus had been eliminated from livestock, thus declaring global freedom from this disease (Hamilton et al., 2017). Circulation of rinderpest virus in endemic regions in wild susceptible species was an important consideration in the eradication campaign, and lack of recognition of wildlife reservoirs was one of the factors to which failure of initial campaigns in the 1960s and 70s was attributed (Morens et al., 2011). Other diseases, such as ASF and FMD, are still endemic and expanding across different regions of the world. FMD is estimated to be endemic in 77% of the global livestock population, in Africa, Asia, and some parts of South America (OIE, 2021a) and ASF is becoming endemic in Africa, Europe, Asia, and some parts of Oceania (OIE, 2021b). Efforts to control or eradicate these diseases are challenging, particularly in those areas where wild reservoir hosts contribute to their maintenance and spread. African swine fever virus (ASFV) has been known for more than a century to be maintained in the soft tick-warthog sylvatic cycle in natural savannah environments in East and Southern Africa. Occasional interactions between ASFV-infected ticks and domestic pigs have facilitated the dissemination of several ASFV genotypes into the domestic pig value-chain in Africa and subsequently into other parts of the world (Dixon et al., 2020). During the currently ongoing pandemic of ASF, the wild boar population in Europe has played a central role in the propagation of the virus into new areas. While most ASF spread appears to occur within domestic pig populations due to anthropogenic factors, incursions of ASFV into low biosecurity domestic pig farming systems from wild boar are also important (Brookes et al., 2021). Likewise, transboundary spread of FMD in susceptible domestic livestock such as cattle and pigs is commonly mediated by anthropogenic factors, such as movement of infected livestock, or the feeding of infected products to susceptible species (Di Nardo et al., 2011). However, in East and Southern Africa, the African buffalo interface plays an important role in maintaining FMD virus (FMDV) strains and disseminating them to adjacent susceptible livestock populations (Jori and Etter, 2016). These examples provide only a snapshot illustration of the potential role of wildlife on livestock disease and demonstrate the importance of the wildlife–livestock interface. At a planetary scale, several factors act as major drivers of increased wildlife–livestock interactions at these interfaces (Magouras et al., 2020). Critical drivers include the need to feed an ever-increasing world human population, which has altered the way in which livestock are farmed, the way in which we interact with the ecosystem, and climate change. These drivers not only increase the intensity and frequency of interactions between wildlife and potential spillover populations (e.g., humans and domesticated animals such as livestock) but also facilitate new transmission pathways for potential emerging pathogens. Some of the impacts of these interactions have been well-described in the literature, particularly those affecting livestock production and health. However, these interactions can also have very significant and devastating effects on wildlife populations and the environment. Importantly, circulation of undetected pathogens in the domestic and wild animal compartments also provides opportunity for the development of potentially dangerous emerging infectious diseases. In this review, we provide an overview of the drivers of wildlife–livestock interactions and their potential impacts on terrestrial livestock production. We define wildlife as any domesticated or non-domesticated species that is free-ranging and does not depend on mankind for food or reproduction. In addition, we present and discuss the major tools and methods to reduce wildlife–livestock contact and to mitigate its health implications, including biosecurity measures and the approaches and potential solutions for improved cohabitation between livestock and wildlife to encourage biodiversity and reduce negative impacts such as disease spillover.

The numerous global outbreaks and continuous reassortments of highly pathogenic avian influenza (HPAI) A(H5N6/H5N8) clade 2.3.4.4 viruses in birds pose a major risk to the public health. We investigated the tropism and innate host responses of 5 recent HPAI A(H5N6/H5N8) avian isolates of clades 2.3.4.4b, e, and h in human airway organoids and primary human alveolar epithelial cells. The HPAI A(H5N6/H5N8) avian isolates replicated productively but with lower competence than the influenza A(H1N1)pdm09, HPAI A(H5N1), and HPAI A(H5N6) isolates from humans in both or either models. They showed differential cellular tropism in human airway organoids; some infected all 4 major epithelial cell types: ciliated cells, club cells, goblet cells, and basal cells. Our results suggest zoonotic potential but low transmissibility of the HPAI A(H5N6/H5N8) avian isolates among humans. These viruses induced low levels of proinflammatory cytokines/chemokines, which are unlikely to contribute to the pathogenesis of severe disease.

There have been five waves of influenza A (H7N9) epidemics in Zhejiang Province between 2013 and 2017. Although the epidemiological characteristics of the five waves have been reported, the molecular genetics aspects, including the phylogeny, evolution, and mutation of hemagglutinin (HA), have not been systematically investigated. A total of 154 H7N9 samples from Zhejiang Province were collected between 2013 and 2017 and sequenced using an Ion Torrent Personal Genome Machine. The starting dates of the waves were 16 March 2013, 1 July 2013, 1 July 2014, 1 July 2015, and 1 July 2016. Single-nucleotide polymorphisms (SNPs) and amino acid mutations were counted after the HA sequences were aligned. The evolution of H7N9 matched the temporal order of the five waves, among which wave 3 played an important role. The 55 SNPs and 14 amino acid mutations with high frequency identified among the five waves revealed the dynamic occurrence of mutation in the process of viral dissemination. Wave 3 contributed greatly to the subsequent epidemic of waves 4 and 5 of H7N9. Compared with wave 1, wave 5 was characterized by more mutations, including A143V and R148K, two mutations that have been reported to weaken the immune response. In addition, some amino acid mutations were observed in wave 5 that led to more lineages. It is necessary to strengthen the surveillance of subsequent H7N9 influenza outbreaks. Supplementary Information The online version contains supplementary material available at 10.1007/s00705-021-05233-5.

Avian influenza (AI) is a respiratory disease complex syndrome recently recorded in vaccinated flocks causing high economic losses. This study aimed to prepare inactivated vaccine from recently isolated field strains [highly pathogenic avian influenza (HPAI) (H5N8) and low pathogenic avian influenza (LPAI) (H9N2)] and compare the efficiency of the two experimental avian influenza vaccines and some commercial avian influenza H5 and H9N2 vaccines in laying hens. The obtained results indicated that the identified experimental vaccines (H5N8 and H9N2) were protected the flocks from AI as compared to commercial H5N1, H5N3, and H9N2 vaccines, which showed a protection level of 80, 70, and 90%, respectively, indicating a high efficacy for the developed vaccines. In addition, it significantly improved the virus shedding, especially when used in booster dose. The experimental vaccines were given high antibody titer higher than commercial vaccine which was reached to 9.3 log2, 9.7log2 for experimental H5N8 vaccine which was significantly higher than and groups 3 and 4 especially at 2nd WPV, while at the 3rd WPV, the significant difference was with group 4 only. The HI titer was 9.3 log2 at 2nd WPV for the experimental H9N2 vaccine that was significantly higher than group 9. In conclusion, the booster dose of the experimental vaccines could elicit strong immunity than single-dose and commercial vaccines.

Background and Aim: Poultry infections with H9N2 avian influenza viruses (AIVs) are endemic in Egypt. This study determined the genetic changes in the sequences of H9N2 AIVs isolated from chicken and quails in Egypt, including determining genetic reassortment and detecting the main genetic changes in hemagglutinin (HA) and neuraminidase (NA) genes. Materials and Methods: Swab samples were collected from chicken and quails, examined through reverse transcription-polymerase chain reaction, and AIVs from positive samples were isolated in embryonated chicken eggs. Complete genome sequencing and phylogenetic analyses were conducted for two H9N2 AIV isolates, and sequences of HA and NA gene segments were analyzed in another two isolates. Results: A novel reassortant virus was identified from a commercial chicken flock (A/chicken/Egypt/374V/2016) and quails from a live bird market (A/quail/Egypt/1253V/2016). The reassortant viruses acquired four genome segments from the classic Egyptian H9N2 viruses (HA, NA, NP, and M) and four segments from Eurasian AIVs (PB2, PB1, PA, and NS). Many genetic changes have been demonstrated in HA and NA genes. The isolated novel reassortant H9N2 virus from quails showed amino acid mutations in the antigenic sites on the globular head of the mature HA monomer matched with the parent Egyptian H9N2 virus. Conclusion: This work described the genetic characterization of a novel reassortment of the H9N2 virus in Egypt. The emergence of new reassorted AIV viruses and genome variability raises the concern of an influenza pandemic with zoonotic potentials.