Showing papers on "Avian Influenza A Virus published in 2020"
TL;DR: Control at the source will be the ultimate and effective option for H9N2 pandemic preparedness, aiming to shed light on the prevention strategies against this strain with pandemic potential.
Abstract: Continuously emergence of human infection with avian influenza A virus poses persistent threat to human health, as illustrated in H5N1, H7N9 and recent surge of H9N2 infections. Long-term prevalence of H9N2 avian influenza A virus in China and adjacent regions favours the interspecies transmissions from avian to human. Establishment of multiple genotypes of H9N2 variants in this region contributes to the emergence of novel H7N9 and H10N8 viruses which caused human fatalities. Recent increasing human infection with H9N2 virus in China highlights the necessity to closely monitor the interspecies transmission events. Available human H9N2 sequences revealed that Y280/G9 lineage was responsible for the most of human cases. Presence of adaptive mutations beyond the human-like receptor binding was indicative of the capacity of readily infecting new hosts without prior adaptation. Moreover, enlarged host range of H9N2 virus in this region substantially increased the transmission among mammals. Meanwhile, serological surveys implied human was more susceptible to H9N2 infection, compared with panzootic H5 and H7 subtype avian influenza virus. Thus, control at the source will be the ultimate and effective option for H9N2 pandemic preparedness. This review comprehensively summarized recent updates on H9N2 human infections, aiming to shed light on the prevention strategies against this strain with pandemic potential.
73 citations
TL;DR: This review focuses on what is known about IAV dynamics in synanthropic hosts that are commonly found on both farms and in nearby habitats, such as fields, lakes, wetlands, or riparian areas occupied by waterfowl or shorebirds.
Abstract: Avian influenza A viruses (IAV) have received significant attention due to the threat they pose to human, livestock, and wildlife health. In this review, we focus on what is known about IAV dynamics in less common avian species that may play a role in trafficking IAVs to poultry operations. Specifically, we focus on synanthropic bird species. Synanthropic species, otherwise known as peridomestic, are species that are ecologically associated with humans and anthropogenically modified landscapes, such as agricultural and urban areas. Aquatic birds such as waterfowl and shorebirds are the species most commonly associated with avian IAVs, and are generally considered the reservoir or maintenance hosts in the natural ecology of these viruses. Waterfowl and shorebirds are occasionally associated with poultry facilities, but are uncommon or absent in many areas, especially large commercial operations. In these cases, spillover hosts that share resources with both maintenance hosts and target hosts such as poultry may play an important role in introducing wild bird viruses onto farms. Consequently, our focus here is on what is known about IAV dynamics in synanthropic hosts that are commonly found on both farms and in nearby habitats, such as fields, lakes, wetlands, or riparian areas occupied by waterfowl or shorebirds.
21 citations
TL;DR: The suppression of NLRP3 inflammasome activation and IL‐1β secretion by PB1‐F2 of highly pathogenic influenza A (H7N9) virus in infected human monocyte‐derived macrophages is demonstrated and has implications in viral pathogenesis and antiviral development.
Abstract: Infection with seasonal as well as highly pathogenic avian influenza A virus (IAV) causes significant morbidity and mortality worldwide. As a major virulence factor, PB1-F2 protein of IAV affects the severity of disease through multiple mechanisms including perturbation of host innate immune response. Macrophages are known to phagocytose extracellular PB1-F2 protein aggregate, leading to hyperactivation of NLRP3 inflammasome and excessive production of IL-1β and IL-18. On the other hand, when expressed intracellularly PB1-F2 suppresses NLRP3 inflammasome maturation. How extracellular and intracellular PB1-F2 orchestrates to drive viral pathogenesis remains unclear. In this study, we demonstrated the suppression of NLRP3 inflammasome activation and IL-1β secretion by PB1-F2 of highly pathogenic influenza A (H7N9) virus in infected human monocyte-derived macrophages. Mechanistically, H7N9 PB1-F2 selectively mitigated RNA-induced NLRP3 inflammasome activation by inhibiting the interaction between NLRP3 and MAVS. Intracellular PB1-F2 of H7N9 virus did not affect extracellular PB1-F2-induced NLRP3 inflammasome maturation. In contrast, PB1-F2 of WSN laboratory strain of human IAV effectively suppressed IL-1β processing and secretion induced by various stimuli including NLRP3, AIM2, and pro-IL-1β. This subtype-specific effect of PB1-F2 on inflammasome activation correlates with the induction of a proinflammatory cytokine storm by H7N9 but not WSN virus. Our findings on selective suppression of MAVS-dependent activation of NLRP3 inflammasome by H7N9 PB1-F2 have implications in viral pathogenesis and antiviral development.
20 citations
TL;DR: Using a mouse model of influenza A virus infection, IFN-κ was one of the earliest responding type I IFNs after infection with H9N2, a low-pathogenic avian influenza Airus, whereas this early induction did not occur upon infection with the epidemic-causing H7N9 virus.
Abstract: Type I interferons (IFNs) are the first line of defense against viral infection. Using a mouse model of influenza A virus infection, we found that IFN-κ was one of the earliest responding type I IFNs after infection with H9N2, a low-pathogenic avian influenza A virus, whereas this early induction did not occur upon infection with the epidemic-causing H7N9 virus. IFN-κ efficiently suppressed the replication of various influenza viruses in cultured human lung cells, and chromodomain helicase DNA binding protein 6 (CHD6) was the major effector for the antiviral activity of IFN-κ, but not for that of IFN-α or IFN-β. The induction of CHD6 required both of the type I IFN receptor subunits IFNAR1 and IFNAR2, the mitogen-activated protein kinase (MAPK) p38, and the transcription factor c-Fos but was independent of signal transducer and activator of transcription 1 (STAT1) activity. In addition, we showed that pretreatment with IFN-κ protected mice from lethal influenza viral challenge. Together, our findings identify an IFN-κ-specific pathway that constrains influenza A virus and provide evidence that IFN-κ may have potential as a preventative and therapeutic agent against influenza A virus.
18 citations
TL;DR: The features of avian ANP32 proteins limited their abilities to support IBV polymerase, which could prevent efficient replication of IBV in chicken cells, and may help to understand the ineffective replication ofIBV in birds.
Abstract: The influenza B virus (IBV) causes seasonal influenza and has accounted for an increasing proportion of influenza outbreaks. IBV mainly causes human infections and has not been found to spread in poultry. The replication mechanism and the determinants of interspecies transmission of IBV are largely unknown. In this study, we found that the host ANP32 proteins are required for the function of the IBV polymerase. Human ANP32A/B strongly supports IBV replication, while ANP32E has a limited role. Unlike human ANP32A/B, chicken ANP32A has low support activity to IBV polymerase because of a unique 33-amino-acid insert, which, in contrast, exhibits species specific support to avian influenza A virus (IAV) replication. Chicken ANP32B and ANP32E have even lower activity compared with human ANP32B/E due to specific amino acid substitutions at sites 129-130. We further revealed that the sites 129-130 affect the binding ability of ANP32B/E to IBV polymerase, while the 33-amino-acid insert of chicken ANP32A reduces its binding stability and affinity. Taken together, the features of avian ANP32 proteins limited their abilities to support IBV polymerase, which could prevent efficient replication of IBV in chicken cells. Our results illustrate roles of ANP32 proteins in supporting IBV replication and may help to understand the ineffective replication of IBV in birds.
13 citations
TL;DR: The results suggest that the role of pigs being the vessel of interspecies transmission should be reconsidered, and the potential of avian H1N1 viruses to infect mammals needs to be characterized in more detail.
Abstract: Pigs play an important role in the interspecies transmission of influenza A viruses (IAV). The porcine airway epithelium contains binding sites for both swine/human IAV (α2,6-linked sialic acids) and avian IAV (α2,3-linked sialic acids) and therefore is suited for adaptation of viruses from other species as suggested by the "mixing vessel theory". Here, we applied well-differentiated swine airway epithelial cells to find out whether efficient infection by avian IAV requires prior adaption. Furthermore, we analyzed the influence of the sialic acid-binding activity and the virus-induced detrimental effects. Surprisingly, an avian IAV H1N1 strain circulating in European poultry and waterfowl shows increased and prolonged viral replication without inducing a strong innate immune response. This virus could infect the lower respiratory tract in our precision cut-lung slice model. Pretreating the cells with poly (I:C) and/or JAK/STAT pathway inhibitors revealed that the interferon-stimulated innate immune response influences the replication of avian IAV in swine airway epitheliums but not that of swine IAV. Further studies indicated that in the infection by IAVs, the binding affinity of sialic acid is not the sole factor affecting the virus infectivity for swine or human airway epithelial cells, whereas it may be crucial in well-differentiated ferret tracheal epithelial cells. Taken together, our results suggest that the role of pigs being the vessel of interspecies transmission should be reconsidered, and the potential of avian H1N1 viruses to infect mammals needs to be characterized in more detail.
11 citations
26 Aug 2020
TL;DR: A previously described biological containment system for IAVs is applied to a 2009 pandemic H1N1 strain and a highly pathogenic H5N 1 strain to study strains with pandemic potential, and it is shown that this method permits safe handling of these pathogens, including gain-of-function variants, without the risk of generating fully infectious viruses.
Abstract: Natural adaptation of an antigenically novel avian influenza A virus (IAV) to be transmitted efficiently in humans has the potential to trigger a devastating pandemic. Understanding viral genetic determinants underlying adaptation is therefore critical for pandemic preparedness, as the knowledge gained enhances surveillance and eradication efforts, prepandemic vaccine design, and efficacy assessment of antivirals. However, this work has risks, as making gain-of-function substitutions in fully infectious IAVs may create a pathogen with pandemic potential. Thus, such experiments must be tightly controlled through physical and biological risk mitigation strategies. Here, we applied a previously described biological containment system for IAVs to a 2009 pandemic H1N1 strain and a highly pathogenic H5N1 strain. The system relies on deletion of the essential viral hemagglutinin (HA) gene, which is instead provided in trans, thereby restricting multicycle virus replication to genetically modified HA-complementing cells. In place of HA, a Renilla luciferase gene is inserted within the viral genome, and a live-cell luciferase substrate allows real-time quantitative monitoring of viral replication kinetics with a high dynamic range. We demonstrate that biologically contained IAV-like particles exhibit wild-type sensitivities to approved antivirals, including oseltamivir, zanamivir, and baloxavir. Furthermore, the inability of these IAV-like particles to genetically acquire the host-encoded HA allowed us to introduce gain-of-function substitutions in the H5 HA gene that promote mammalian transmissibility. Biologically contained "transmissible" H5N1 IAV-like particles exhibited wild-type sensitivities to approved antivirals, to the fusion inhibitor S20, and to neutralization by existing H5 monoclonal and polyclonal sera. This work represents a proof of principle that biologically contained IAV systems can be used to safely conduct selected gain-of-function experiments.IMPORTANCE Understanding how animal influenza viruses can adapt to spread in humans is critical to prepare for, and prevent, new pandemics. However, working safely with pathogens that have pandemic potential requires tight regulation and the use of high-level physical and biological risk mitigation strategies to stop accidental loss of containment. Here, we used a biological containment system for influenza viruses to study strains with pandemic potential. The system relies on deletion of the essential HA gene from the viral genome and its provision by a genetically modified cell line, to which virus propagation is therefore restricted. We show that this method permits safe handling of these pathogens, including gain-of-function variants, without the risk of generating fully infectious viruses. Furthermore, we demonstrate that this system can be used to assess virus sensitivity to both approved and experimental drugs, as well as the antigenic profile of viruses, important considerations for evaluating prepandemic vaccine and antiviral strategies.
9 citations
TL;DR: Evidence of aerosolized avian influenza A viruses was detected in LBMs and in the respiratory tracts of market workers, indicating exposure and potential for infection.
Abstract: In response to unusual crow die‐offs from avian influenza A(H5N1) virus infection during January‐February 2017 in Dhaka, Bangladesh, a One Health team assessed potential infection risks in live bird markets (LBMs). Evidence of aerosolized avian influenza A viruses was detected in LBMs and in the respiratory tracts of market workers, indicating exposure and potential for infection. This study highlighted the importance of surveillance platforms with a coordinated One Health strategy to investigate and mitigate zoonotic risk.
9 citations
TL;DR: The prevalence of influenza A viruses in wild birds (waterbirds and land birds; resident and migratory) in eastern Mexico, where the three main North American migration flyways converge and where there was no previous information on this subject, was estimated.
Abstract: Aquatic wild birds, especially waterfowl, have been long considered the main reservoirs of the avian influenza A virus; however, recent surveys have found an important prevalence of these viruses among land birds as well. Migration has been suggested as an important factor in the avian influenza virus dissemination. We aimed to estimate the prevalence of influenza A viruses in wild birds (waterbirds and land birds; resident and migratory) in eastern Mexico, where the three main North American migration flyways converge and where there was no previous information on this subject. We detected influenza with reverse transcription coupled with a PCR approach. Of the 534 birds sampled between 2010 and 2012, we detected the influenza A virus in a high proportion of birds (39%). Prevalence was particularly high in land birds (49%) when compared to aquatic birds (26%); there was no difference in overall prevalence between resident (39%) and migratory birds (39%). The high prevalence of the avian influenza virus in land birds was noteworthy in the innermost sampling areas in northern Mexico (Coahuila [82%] and Nuevo Leon [43%]).
8 citations
TL;DR: The potential risks that synanthropic mammals could pose by trafficking IAVs to poultry operations based on current and historic literature are summarized and discussed.
Abstract: The potential role of wild mammals in the epidemiology of influenza A viruses (IAVs) at the farm-side level has gained increasing consideration over the past two decades. In some instances, select mammals may be more likely to visit riparian areas (both close and distant to farms) as well as poultry farms, as compared to traditional reservoir hosts, such as waterfowl. Of significance, many mammalian species can successfully replicate and shed multiple avian IAVs to high titers without prior virus adaptation and often can shed virus in greater quantities than synanthropic avian species. Within this review, we summarize and discuss the potential risks that synanthropic mammals could pose by trafficking IAVs to poultry operations based on current and historic literature.
8 citations
TL;DR: This work shows that a combination of electrostatics and Normal Modes Analysis can also identify fingerprints specific to high and low pathogenicity, which may help in surveillance and vaccine development.
Abstract: Type A influenza viruses circulate and spread among wild birds and mostly consist of low pathogenic strains. However, fast genome variation timely results in the insurgence of high pathogenic strains, which when infecting poultry birds may cause a million deaths and strong commercial damage. More importantly, the host shift may concern these viruses and sustained human-to-human transmission may result in a dangerous pandemic outbreak. Therefore, fingerprints specific to either low or high pathogenic strains may represent a very important tool for global surveillance. We combined Normal Modes Analysis and surface electrostatic analysis of a mixed strain dataset of influenza A virus haemagglutinins from high and low pathogenic strains in order to infer specific fingerprints. Normal Modes Analysis sorted the strains in two different, homogeneous clusters; sorting was independent of clades and specific instead to high vs low pathogenicity. A deeper analysis of fluctuations and flexibility regions unveiled a special role for the 110-helix region. Specific sorting was confirmed by surface electrostatics analysis, which further allowed to focus on regions and mechanisms possibly crucial to the low-to-high transition. Evidence from previous work demonstrated that changes in surface electrostatics are associated with the evolution and spreading of avian influenza A virus clades, and seemingly involved also in the avian to mammalian host shift. This work shows that a combination of electrostatics and Normal Modes Analysis can also identify fingerprints specific to high and low pathogenicity. The possibility to predict which specific mutations may result in a shift to high pathogenicity may help in surveillance and vaccine development.
TL;DR: It is demonstrated that H5N1 (Clade 2.2.1.2) reassortants carrying internal proteins-encoding segments of G1-like H9N2 viruses can emerge and may gain improved replication fitness and augment the zoonotic potential of H 5N1 viruses, especially by acquiring unique mammalian-like aa signatures.
Abstract: Egypt is a hotspot for H5- and H9-subtype avian influenza A virus (AIV) infections and co-infections in poultry by both subtypes have been frequently reported. However, natural genetic reassortment of these subtypes has not been reported yet. Here, we evaluated the genetic compatibility and replication efficiency of reassortants between recent isolates of an Egyptian H5N1 and a H9N2 AIV (H5N1EGY and H9N2EGY). All internal viral proteins-encoding segments of the contemporaneous G1-like H9N2EGY, expressed individually and in combination in the genetic background of H5N1EGY, were genetically compatible with the other H5N1EGY segments. At 37 °C the replication efficiencies of H5N1EGY reassortants expressing the H9N2EGY polymerase subunits PB2 and PA (H5N1PB2-H9N2EGY, H5N1PA-H9N2EGY) were higher than the wild-type H5N1EGY in Madin-Darby canine kidney (MDCK-II) cells. This could not be correlated to viral polymerase activity as this was found to be improved for H5N1PB2-H9N2EGY, but reduced for H5N1PA-H9N2EGY. At 33 °C and 39 °C, H5N1PB2-H9N2EGY and H5N1PA-H9N2EGY replicated to higher levels than the wild-type H5N1EGY in human Calu-3 and A549 cell lines. Nevertheless, in BALB/c mice both reassortants caused reduced mortality compared to the wild-type H5N1EGY. Genetic analysis of the polymerase-encoding segments revealed that the PAH9N2EGY and PB2H9N2EGY encode for a distinct uncharacterized mammalian-like variation (367K) and a well-known mammalian signature (591K), respectively. Introducing the single substitution 367K into the PA of H5N1EGY enabled the mutant virus H5N1PA-R367K to replicate more efficiently at 37 °C in primary human bronchial epithelial (NHBE) cells and also in A549 and Calu-3 cells at 33 °C and 39 °C. Furthermore, H5N1PA-R367K caused higher mortality in BALB/c mice. These findings demonstrate that H5N1 (Clade 2.2.1.2) reassortants carrying internal proteins-encoding segments of G1-like H9N2 viruses can emerge and may gain improved replication fitness. Thereby such H5N1/H9N2 reassortants could augment the zoonotic potential of H5N1 viruses, especially by acquiring unique mammalian-like aa signatures.
TL;DR: It is suggested that during infection of humans, H5 viruses evolved to adapt to their new host environment and that the sites of adaptive/parallel evolution might play a role in crossing the species barrier and the response to new selection pressure.
TL;DR: High-throughput RNA-sequencing technology at the transcriptome level suggests that H9N2 virus infection may enhance the signal transduction, and innate immune responses in chicken DCs, but impair their metabolic functions and antigen-presenting responses, which provide helpful insight into the pathogenesis of H 9N2 AIVs in chickens and managing this infection in poultry farms.
TL;DR: A systemic review regarding virus-induced pathogenesis, vaccine development, and diagnosis of H7N9 AIV infection in humans finds mechanisms via which the virus induces severe syndromes remain unclear.
Abstract: H7N9 avian influenza virus (AIV) caused human infections in 2013 in China. Phylogenetic analyses indicate that H7N9 AIV is a novel reassortant strain with pandemic potential. We conducted a systemi...
TL;DR: Investigation of the interactions between H9N2 hemagglutinin and the mammalian receptor, the polysaccharide α-2,6-linked lactoseries tetrasaccharide c, at the atomic level provided a way to understand the adaptive mechanisms of H 9N2 viruses, which may help predict its propensity to spread in mammals.
TL;DR: The results suggest that the clinical signs observed in macaques infected with the NA292K virus are caused by the NA 292K virus and theNA292R virus and that the virus withNA292K may not replicate continuously in the upper respiratory tract of patients without treatment as effectively as the wild-type virus.
05 Mar 2020
TL;DR: The complete genome sequence of a highly pathogenic strain of avian influenza A virus/domestic goose/Pavlodar/1-05 (H5N1) (GS/1/05), which belongs to clade 2.2.1, is presented.
Abstract: Here, we present the complete genome sequence of a highly pathogenic strain of avian influenza A virus/domestic goose/Pavlodar/1/05 (H5N1) (GS/1/05), which belongs to clade 2.2. This strain of the influenza virus was isolated in northern Kazakhstan in 2005.
09 Apr 2020
TL;DR: In this article, the 1st order statistics and correlation functions of 2D speckle structures corresponding to the several nucleotide sequences of HPAIV have been analyzed, and the GB-speckles, generated for highly-pathogenic strains A/Gs/HK/739.2/02 (H5N1) and A/chicken/Ganzhou/GZ43/2016(H3N2)) segment 6 neuraminidase (NA) gene, Influenza A virus A/pheasant/Korea/LBM180/
Abstract: Gene-based speckles (GB-speckles) have been implied for interpretation of nucleotide sequences of the target genes of HPAIV. The 1st order statistics and correlation functions of 2D speckle structures corresponding to the several nucleotide sequences of HPAIV have been analyzed. The GB-speckles, generated for highly-pathogenic strains A/Gs/HK/739.2/02 (H5N1) and HPAIV (A/Chicken/Hong Kong/YU562/01 (H5N1)) neuraminidase (NA) have been compared with the speckles, related to three low-pathogenic strains (Influenza A virus (A/chicken/Ganzhou/GZ43/2016(H3N2)) segment 6 neuraminidase (NA) gene, Influenza A virus A/pheasant/Korea/LBM180/2008(H9N2)) segment 6 neuraminidase (NA) gene, and Influenza A virus A/chicken/Alkharj/910/2018(H5N8)) segment 6 neuraminidase (NA) gene). Perspectives of fast and precise discrimination of nucleotide sequences of the different avian influenza strains, including HPAIV variants, based on GBspeckles, are demonstrated.