scholarly journals Critical Influenza-Like Illness in a Nine-Year-Old Associated With a Poultry-Origin H9N2 Avian Influenza Virus: Risk Assessment and Zoonotic Potential

2021 ◽  
Vol 1 ◽  
Author(s):  
Fengming Zhao ◽  
Yuqing Wang ◽  
Liping Chen ◽  
Xinxing Zhang ◽  
Mariette Ducatez ◽  
...  
Keyword(s):  
Risk Assessment ◽  
Influenza Virus ◽  
Avian Influenza ◽  
Avian Influenza Virus ◽  
Laboratory Data ◽  
Influenza Viruses ◽  
Type I ◽  
Influenza Like Illness ◽  
Syncytial Virus

Subtype H9N2 avian influenza viruses (AIV), now the predominant avian influenza virus subtype in poultry in China, cause sporadic human infections manifesting as mild influenza-like illness. We isolated an H9N2 AIV from a critical case of respiratory illness in a 9-year-old with no underlying conditions. As this virus was associated with critical illness, we conducted a risk assessment to determine its mammalian pathogenicity. Clinical and laboratory data were collected from hospital records. A/Suzhou/GIRD01/2019 (H9N2) (GIRD01) was isolated from a throat swab and used in risk-assessment studies in comparison to prototypical and contemporary H9N2 AIVs and contemporary seasonal subtype H1N1 and H3N2 influenza viruses. The patient presented with fever, vomiting but rapidly declined to progressive wheezing followed by dyspnea. The patient was admitted to the intensive care unit and placed on mechanical ventilation. A diagnosis of pneumonia and type I respiratory failure was made. Viral RNA was detected in the bronchiolavelolar lavage and anal swab specimens, suggesting lower lung and extrapulmonary involvement. Respiratory syncytial virus was also detected by immunofluorescence in bronchiolavelolar lavage. Following an aggressive regimen of antiviral and antibacterial therapy, the patient recovered and was discharged from hospital after 13 days. GIRD01 was closely related to poultry-origin H9N2 AIVs in the area and contained several known markers of mammalian pathogenicity. GIRD01 also showed a strong affinity for mammalian-type over avian-type sialic acids. GIRD01 replicated more efficiently compared to older H9N2 viruses and contemporary seasonal viruses in vitro and produced asymptomatic infections in mice. In summary, GIRD01 was well-adapted to replication in in vitro and in vivo mammalian models but was not more pathogenic compared to similar contemporary strains of H9N2 AIVs. Therefore, these viruses may pose a risk of causing severe respiratory disease in humans.

scholarly journals Knockout of IRF7 Highlights its Modulator Function of Host Response Against Avian Influenza Virus and the Involvement of MAPK and TOR Signaling Pathways in Chicken

Genes ◽  
2020 ◽  
Vol 11 (4) ◽  
pp. 385
Author(s):  
Tae Hyun Kim ◽  
Colin Kern ◽  
Huaijun Zhou
Keyword(s):  
Influenza Virus ◽  
Avian Influenza ◽  
Avian Influenza Virus ◽  
Signaling Pathways ◽  
Cell Lines ◽  
Host Response ◽  
Antiviral Response ◽  
Influenza Viruses ◽  
Interferon Response ◽  
Type I

Interferon regulatory factor 7 (IRF7) is known as the master transcription factor of the type I interferon response in mammalian species along with IRF3. Yet birds only have IRF7, while they are missing IRF3, with a smaller repertoire of immune-related genes, which leads to a distinctive immune response in chickens compared to in mammals. In order to understand the functional role of IRF7 in the regulation of the antiviral response against avian influenza virus in chickens, we generated IRF7-/- chicken embryonic fibroblast (DF-1) cell lines and respective controls (IRF7wt) by utilizing the CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9) system. IRF7 knockout resulted in increased viral titers of low pathogenic avian influenza viruses. Further RNA-sequencing performed on H6N2-infected IRF7-/- and IRF7wt cell lines revealed that the deletion of IRF7 resulted in the significant down-regulation of antiviral effectors and the differential expression of genes in the MAPK (mitogen-activated protein kinase) and mTOR (mechanistic target of rapamycin) signaling pathways. Dynamic gene expression profiling of the host response between the wildtype and IRF7 knockout revealed potential signaling pathways involving AP1 (activator protein 1), NF-κB (nuclear factor kappa B) and inflammatory cytokines that may complement chicken IRF7. Our findings in this study provide novel insights that have not been reported previously, and lay a solid foundation for enhancing our understanding of the host antiviral response against the avian influenza virus in chickens.

scholarly journals A Unique Multibasic Proteolytic Cleavage Site and Three Mutations in the HA2 Domain Confer High Virulence of H7N1 Avian Influenza Virus in Chickens

2015 ◽  
Vol 90 (1) ◽  
pp. 400-411 ◽  
Author(s):  
El-Sayed M. Abdelwhab ◽  
Jutta Veits ◽  
Kerstin Tauscher ◽  
Mario Ziller ◽  
Jens P. Teifke ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Avian Influenza ◽  
Avian Influenza Virus ◽  
Cleavage Site ◽  
Influenza Viruses ◽  
Highly Pathogenic ◽  
Systemic Spread ◽  
H7n1 Virus

ABSTRACT In 1999, after circulation for a few months in poultry in Italy, low-pathogenic (LP) avian influenza (AI) H7N1 virus mutated into a highly pathogenic (HP) form by acquisition of a unique multibasic cleavage site (mCS), PEIPKGSRVRR*GLF (asterisk indicates the cleavage site), in the hemagglutinin (HA) and additional alterations with hitherto unknown biological function. To elucidate these virulence-determining alterations, recombinant H7N1 viruses carrying specific mutations in the HA of LPAI A/chicken/Italy/473/1999 virus (Lp) and HPAI A/chicken/Italy/445/1999 virus (Hp) were generated. Hp with a monobasic CS or carrying the HA of Lp induced only mild or no disease in chickens, thus resembling Lp. Conversely, Lp with the HA of Hp was as virulent and transmissible as Hp. While Lp with a multibasic cleavage site (Lp_CS445) was less virulent than Hp, full virulence was exhibited when HA2 was replaced by that of Hp. In HA2, three amino acid differences consistently detected between LP and HP H7N1 viruses were successively introduced into Lp_CS445. Q450L in the HA2 stem domain increased virulence and transmission but was detrimental to replication in cell culture, probably due to low-pH activation of HA. A436T and/or K536R restored viral replication in vitro and in vivo . Viruses possessing A436T and K536R were observed early in the HPAI outbreak but were later superseded by viruses carrying all three mutations. Together, besides the mCS, stepwise mutations in HA2 increased the fitness of the Italian H7N1 virus in vivo . The shift toward higher virulence in the field was most likely gradual with rapid optimization. IMPORTANCE In 1999, after 9 months of circulation of low-pathogenic (LP) avian influenza virus (AIV), a devastating highly pathogenic (HP) H7N1 AIV emerged in poultry, marking the largest epidemic of AIV reported in a Western country. The HPAIV possessed a unique multibasic cleavage site (mCS) complying with the minimum motif for HPAIV. The main finding in this report is the identification of three mutations in the HA2 domain that are required for replication and stability, as well as for virulence, transmission, and tropism of H7N1 in chickens. In addition to the mCS, Q450L was required for full virulence and transmissibility of the virus. Nonetheless, it was detrimental to virus replication and required A436T and/or K536R to restore replication, systemic spread, and stability. These results are important for better understanding of the evolution of highly pathogenic avian influenza viruses from low-pathogenic precursors.

scholarly journals Genetic Characterization and Pathogenesis of Avian Influenza Virus H7N3 Isolated from Spot-Billed Ducks in South Korea, Early 2019

Viruses ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 856
Author(s):  
Thuy-Tien Thi Trinh ◽  
Indira Tiwari ◽  
Kaliannan Durairaj ◽  
Bao Tuan Duong ◽  
Anh Thi Viet Nguyen ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Amino Acid ◽  
Avian Influenza ◽  
South Korea ◽  
Avian Influenza Virus ◽  
Post Infection ◽  
Influenza Viruses ◽  
Avian Influenza Viruses ◽  
Highly Pathogenic

Low-pathogenicity avian influenza viruses (LPAIV) introduced by migratory birds circulate in wild birds and can be transmitted to poultry. These viruses can mutate to become highly pathogenic avian influenza viruses causing severe disease and death in poultry. In March 2019, an H7N3 avian influenza virus—A/Spot-billed duck/South Korea/WKU2019-1/2019 (H7N3)—was isolated from spot-billed ducks in South Korea. This study aimed to evaluate the phylogenetic and mutational analysis of this isolate. Molecular analysis revealed that the genes for HA (hemagglutinin) and NA (neuraminidase) of this strain belonged to the Central Asian lineage, whereas genes for other internal proteins such as polymerase basic protein 1 (PB1), PB2, nucleoprotein, polymerase acidic protein, matrix protein, and non-structural protein belonged to that of the Korean lineage. In addition, a monobasic amino acid (PQIEPR/GLF) at the HA cleavage site, and the non-deletion of the stalk region in the NA gene indicated that this isolate was a typical LPAIV. Nucleotide sequence similarity analysis of HA revealed that the highest homology (99.51%) of this isolate is to that of A/common teal/Shanghai/CM1216/2017 (H7N7), and amino acid sequence of NA (99.48%) was closely related to that of A/teal/Egypt/MB-D-487OP/2016 (H7N3). An in vitro propagation of the A/Spot-billed duck/South Korea/WKU2019-1/2019(H7N3) virus showed highest (7.38 Log10 TCID50/mL) virus titer at 60 h post-infection, and in experimental mouse lungs, the virus was detected at six days’ post-infection. Our study characterizes genetic mutations, as well as pathogenesis in both in vitro and in vivo model of a new Korea H7N3 viruses in 2019, carrying multiple potential mutations to become highly pathogenic and develop an ability to infect humans; thus, emphasizing the need for routine surveillance of avian influenza viruses in wild birds.

scholarly journals Characterization of the In Vitro and In Vivo Efficacy of Baloxavir Marboxil against the H5 Highly Pathogenic Avian Influenza Virus Infection

2021 ◽  
Author(s):  
Keiichi Taniguchi ◽  
Yoshinori Ando ◽  
Masanori Kobayashi ◽  
Shinsuke Toba ◽  
Haruaki Nobori ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Avian Influenza ◽  
Avian Influenza Virus ◽  
Highly Pathogenic Avian Influenza ◽  
Influenza Virus Infection ◽  
Highly Pathogenic ◽  
Pathogenic Avian Influenza ◽  
Antiviral Efficacy ◽  
Pathogenic Avian Influenza Virus

Human infections with the H5 highly pathogenic avian influenza virus (HPAIV) sporadically threatens public health. The susceptibility of HPAIVs to baloxavir acid (BXA), which is a new class of inhibitor for the influenza virus cap-dependent endonuclease, has been confirmed in vitro, but has not yet been characterized fully. Here, the efficacy of BXA against HPAIVs, including recent H5N8 variants in vitro was assessed. The antiviral efficacy of baloxavir marboxil (BXM) in H5N1 virus-infected mice was also investigated. BXA exhibited similar in vitro activities against H5N1, H5N6, and H5N8 variants tested to those of seasonal and other zoonotic strains. BXM monotherapy in mice infected with the H5N1 HPAIV clinical isolate; A/Hong Kong/483/1997 (H5N1) strain, also caused a significant reduction in viral titers in the lungs, brains, and kidneys, followed by prevention of acute lung inflammation and improvement of mortality compared with oseltamivir phosphate (OSP). Furthermore, combination treatments with BXM and OSP, using a 48-hour delayed treatment model showed a more potent effect on viral replication in organs, accompanied by improved survival compared to BXM or OSP monotherapy. From each test, no resistant virus (e.g., I38T in the PA) emerged in any BXM-treated mouse. These results therefore support the conclusion that BXM has potent antiviral efficacy against H5 HPAIV infections.

scholarly journals Detection of avian influenza virus: a comparative study of the in silico and in vitro performances of current RT-qPCR assays

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Andrea Laconi ◽  
Andrea Fortin ◽  
Giulia Bedendo ◽  
Akihiro Shibata ◽  
Yoshihiro Sakoda ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Avian Influenza ◽  
Comparative Study ◽  
Avian Influenza Virus ◽  
In Silico ◽  
Influenza Virus A

scholarly journals Genetic Characterization of Avian Influenza A (H11N9) Virus Isolated from Mandarin Ducks in South Korea in 2018

Viruses ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 203
Author(s):  
Hien Thi Tuong ◽  
Ngoc Minh Nguyen ◽  
Haan Woo Sung ◽  
Hyun Park ◽  
Seon-Ju Yeo
Keyword(s):  
Influenza Virus ◽  
Amino Acid ◽  
Avian Influenza ◽  
South Korea ◽  
Avian Influenza Virus ◽  
Influenza A ◽  
Sequence Similarity ◽  
Basic Amino Acid ◽  
Wild Birds

In July 2018, a novel avian influenza virus (A/Mandarin duck/South Korea/KNU18-12/2018(H11N9)) was isolated from Mandarin ducks in South Korea. Phylogenetic and molecular analyses were conducted to characterize the genetic origins of the H11N9 strain. Phylogenetic analysis indicated that eight gene segments of strain H11N9 belonged to the Eurasian lineages. Analysis of nucleotide sequence similarity of both the hemagglutinin (HA) and neuraminidase (NA) genes revealed the highest homology with A/duck/Kagoshima/KU57/2014 (H11N9), showing 97.70% and 98.00% nucleotide identities, respectively. Additionally, internal genes showed homology higher than 98% compared to those of other isolates derived from duck and wild birds. Both the polymerase acidic (PA) and polymerase basic 1 (PB1) genes were close to the H5N3 strain isolated in China; whereas, other internal genes were closely related to that of avian influenza virus in Japan. A single basic amino acid at the HA cleavage site (PAIASR↓GLF), the lack of a five-amino acid deletion (residue 69–73) in the stalk region of the NA gene, and E627 in the polymerase basic 2 (PB2) gene indicated that the A/Mandarin duck/South Korea/KNU18-12/2018(H11N9) isolate was a typical low-pathogenicity avian influenza. In vitro viral replication of H11N9 showed a lower titer than H1N1 and higher than H9N2. In mice, H11N9 showed lower adaptation than H1N1. The novel A/Mandarin duck/South Korea/KNU18-12/2018(H11N9) isolate may have resulted from an unknown reassortment through the import of multiple wild birds in Japan and Korea in approximately 2016–2017, evolving to produce a different H11N9 compared to the previous H11N9 in Korea (2016). Further reassortment events of this virus occurred in PB1 and PA in China-derived strains. These results indicate that Japanese- and Chinese-derived avian influenza contributes to the genetic diversity of A/Mandarin duck/South Korea/KNU18-12/2018(H11N9) in Korea.

scholarly journals Swine ANP32A Supports Avian Influenza Virus Polymerase

2020 ◽  
Vol 94 (12) ◽  
Author(s):  
Thomas P. Peacock ◽  
Olivia C. Swann ◽  
Hamish A. Salvesen ◽  
Ecco Staller ◽  
P. Brian Leung ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Avian Influenza ◽  
Avian Influenza Virus ◽  
Virus Replication ◽  
Mammalian Species ◽  
Gene Mutations ◽  
Influenza Viruses ◽  
Avian Influenza Viruses ◽  
2009 H1n1 ◽  
Mixing Vessels

ABSTRACT Avian influenza viruses occasionally infect and adapt to mammals, including humans. Swine are often described as “mixing vessels,” being susceptible to both avian- and human-origin viruses, which allows the emergence of novel reassortants, such as the precursor to the 2009 H1N1 pandemic. ANP32 proteins are host factors that act as influenza virus polymerase cofactors. In this study, we describe how swine ANP32A, uniquely among the mammalian ANP32 proteins tested, supports the activity of avian-origin influenza virus polymerases and avian influenza virus replication. We further show that after the swine-origin influenza virus emerged in humans and caused the 2009 pandemic, it evolved polymerase gene mutations that enabled it to more efficiently use human ANP32 proteins. We map the enhanced proviral activity of swine ANP32A to a pair of amino acids, 106 and 156, in the leucine-rich repeat and central domains and show these mutations enhance binding to influenza virus trimeric polymerase. These findings help elucidate the molecular basis for the mixing vessel trait of swine and further our understanding of the evolution and ecology of viruses in this host. IMPORTANCE Avian influenza viruses can jump from wild birds and poultry into mammalian species such as humans or swine, but they only continue to transmit if they accumulate mammalian adapting mutations. Pigs appear uniquely susceptible to both avian and human strains of influenza and are often described as virus “mixing vessels.” In this study, we describe how a host factor responsible for regulating virus replication, ANP32A, is different between swine and humans. Swine ANP32A allows a greater range of influenza viruses, specifically those from birds, to replicate. It does this by binding the virus polymerase more tightly than the human version of the protein. This work helps to explain the unique properties of swine as mixing vessels.

scholarly journals Characterization of Host Responses against a Recombinant Fowlpox Virus-Vectored Vaccine Expressing the Hemagglutinin Antigen of an Avian Influenza Virus

2010 ◽  
Vol 17 (3) ◽  
pp. 454-463 ◽  
Author(s):  
Hamid R. Hghihghi ◽  
Leah R. Read ◽  
Hakimeh Mohammadi ◽  
Yanlong Pei ◽  
Claudia Ursprung ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Avian Influenza ◽  
Immune Responses ◽  
Avian Influenza Virus ◽  
Cultured Cells ◽  
Type I Interferons ◽  
Host Responses ◽  
Type I ◽  
Fowlpox Virus ◽  
Time Points

ABSTRACT There currently are commercial fowlpox virus (FPV)-vectored vaccines for use in chickens, including TROVAC-AIV H5, which expresses the hemagglutinin (HA) antigen of an avian influenza virus and can confer immunity against avian influenza in chickens. Despite the use of recombinant FPV (rFPV) for vaccine delivery, very little is known about the immune responses generated by these viruses in chickens. The present study was designed to investigate host responses to rFPV in vivo and in vitro. In cultured cells infected with TROVAC-AIV H5, there was an early increase in the expression of type I interferons (IFN), Toll-like receptors 3 and 7 (TLR3 and TLR7, respectively), TRIF, and MyD88, which was followed by a decrease in the expression of these genes at later time points. There also was an increase in the expression of interleukin-1β (IL-1β), IL-8, and beta-defensin genes at early time points postinfection. In chickens immunized with TROVAC-AIV H5, there was higher expression of IFN-γ and IL-10 at day 5 postvaccination in spleen of vaccinated birds than in that of control birds. We further investigated the ability of the vaccine to induce immune responses against the HA antigen and discovered that there was a cell-mediated response elicited in vaccinated chickens against this antigen. The findings of this study demonstrate that FPV-vectored vaccines can elicit a repertoire of responses marked by the early expression of TLRs, type I interferons, and proinflammatory cytokines, as well as cytokines associated with adaptive immune responses. This study provides a platform for designing future generations of rFPV-vectored vaccines.

scholarly journals A review of H5Nx avian influenza viruses

2019 ◽  
Vol 7 ◽  
pp. 251513551882162 ◽  
Author(s):  
Ivette A. Nuñez ◽  
Ted M. Ross
Keyword(s):  
Influenza Virus ◽  
Avian Influenza ◽  
Avian Influenza Virus ◽  
Highly Pathogenic Avian Influenza ◽  
Influenza Viruses ◽  
Avian Influenza Viruses ◽  
Highly Pathogenic ◽  
Bird Populations ◽  
Pathogenic Avian Influenza ◽  
Pathogenic Avian Influenza Virus

Highly pathogenic avian influenza viruses (HPAIVs), originating from the A/goose/Guangdong/1/1996 H5 subtype, naturally circulate in wild-bird populations, particularly waterfowl, and often spill over to infect domestic poultry. Occasionally, humans are infected with HPAVI H5N1 resulting in high mortality, but no sustained human-to-human transmission. In this review, the replication cycle, pathogenicity, evolution, spread, and transmission of HPAIVs of H5Nx subtypes, along with the host immune responses to Highly Pathogenic Avian Influenza Virus (HPAIV) infection and potential vaccination, are discussed. In addition, the potential mechanisms for Highly Pathogenic Avian Influenza Virus (HPAIV) H5 Reassorted Viruses H5N1, H5N2, H5N6, H5N8 (H5Nx) viruses to transmit, infect, and adapt to the human host are reviewed.

scholarly journals Tropism and Infectivity of a Seasonal A(H1N1) and a Highly Pathogenic Avian A(H5N1) Influenza Virus in Primary Differentiated Ferret Nasal Epithelial Cell Cultures

2019 ◽  
Vol 93 (10) ◽  
Author(s):  
Hui Zeng ◽  
Cynthia S. Goldsmith ◽  
Amrita Kumar ◽  
Jessica A. Belser ◽  
Xiangjie Sun ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Virus Infection ◽  
Avian Influenza ◽  
H5n1 Virus ◽  
H1n1 Virus ◽  
Influenza Virus Infection ◽  
Influenza Viruses ◽  
Host Interactions ◽  
Culture Model

ABSTRACTFerrets represent an invaluable animal model to study influenza virus pathogenesis and transmission. To further characterize this model, we developed a differentiated primary ferret nasal epithelial cell (FNEC) culture model for investigation of influenza A virus infection and virus-host interactions. This well-differentiated culture consists of various cell types, a mucociliary clearance system, and tight junctions, representing the nasal ciliated pseudostratified respiratory epithelium. Both α2,6-linked and α2,3-linked sialic acid (SA) receptors, which preferentially bind the hemagglutinin (HA) of human and avian influenza viruses, respectively, were detected on the apical surface of the culture with different cellular tropisms. In accordance with the distribution of SA receptors, we observed that a pre-2009 seasonal A(H1N1) virus infected both ciliated and nonciliated cells, whereas a highly pathogenic avian influenza (HPAI) A(H5N1) virus primarily infected nonciliated cells. Transmission electron microscopy revealed that virions were released from or associated with the apical membranes of ciliated, nonciliated, and mucin-secretory goblet cells. Upon infection, the HPAI A(H5N1) virus replicated to titers higher than those of the human A(H1N1) virus at 37°C; however, replication of the A(H5N1) virus was significantly attenuated at 33°C. Furthermore, we found that infection with the A(H5N1) virus induced higher expression levels of immune mediator genes and resulted in more cell damage/loss than with the human A(H1N1) virus. This primary differentiated FNEC culture model, recapitulating the structure of the nasal epithelium, provides a useful model to bridgein vivoandin vitrostudies of cellular tropism, infectivity, and pathogenesis of influenza viruses during the initial stages of infection.IMPORTANCEAlthough ferrets serve as an important model of influenza virus infection, much remains unknown about virus-host interactions in this species at the cellular level. The development of differentiated primary cultures of ferret nasal epithelial cells is an important step toward understanding cellular tropism and the mechanisms of influenza virus infection and replication in the airway milieu of this model. Using lectin staining and microscopy techniques, we characterized the sialic acid receptor distribution and the cellular composition of the culture model. We then evaluated the replication of and immune response to human and avian influenza viruses at relevant physiological temperatures. Our findings offer significant insight into this first line of defense against influenza virus infection and provide a model for the evaluation of emerging influenza viruses in a well-controlledin vitroenvironmental setting.

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