scholarly journals New hemagglutinin dual-receptor-binding pattern of a human-infecting influenza A (H7N9) virus isolated after fifth epidemic wave

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Lei Guo ◽  
Nan Li ◽  
Wenlong Li ◽  
Jienan Zhou ◽  
Ruotong Ning ◽  
...  
Keyword(s):  
Receptor Binding ◽  
Influenza A ◽  
Human Infection ◽  
Binding Property ◽  
H7n9 Virus ◽  
Receptor Binding Site ◽  
Highly Pathogenic ◽  
Influenza H7n9 Virus ◽  
Epidemic Wave ◽  
Human Receptor

Abstract Since 2013, influenza H7N9 virus has caused five epidemic waves of human infection. The virus evolved from low pathogenic to highly pathogenic in wave 5, 2017, while the prevalence of host receptor-binding tropism in human-infecting viruses maintained dual-receptor-binding property with preference for avian receptor. A human-infecting H7N9 virus was isolated after the fifth epidemic wave and possessed an avian and human dual-receptor specificity, with a moderately higher affinity for human receptor binding. A V186I (H3 numbering) substitution in the receptor-binding site of the hemagglutinin (HA) molecule is responsible for the alteration of the dual-receptor-binding tropism. Viral strains which contain I186 amino acid of avian- and human-infecting H7N9 viruses were all isolated during or after wave 5, and their HA genes clustered in a same phylogenetic clade together with 2018–9 H7N9 isolates, highlights a new evolutionary path for human adaption of natural H7N9 viruses.

scholarly journals Biological characterisation of the emerged highly pathogenic avian influenza (HPAI) A(H7N9) viruses in humans, in mainland China, 2016 to 2017

2017 ◽  
Vol 22 (19) ◽  
Author(s):  
Wenfei Zhu ◽  
Jianfang Zhou ◽  
Zi Li ◽  
Lei Yang ◽  
Xiyan Li ◽  
...  
Keyword(s):  
Avian Influenza ◽  
Influenza A ◽  
Highly Pathogenic Avian Influenza ◽  
Mainland China ◽  
H7n9 Virus ◽  
Highly Pathogenic ◽  
Pathogenic Avian Influenza ◽  
Binding Preference ◽  
Severe Infections ◽  
Epidemic Wave

With no or low virulence in poultry, avian influenza A(H7N9) virus has caused severe infections in humans. In the current fifth epidemic wave, a highly pathogenic avian influenza (HPAI) H7N9 virus emerged. The insertion of four amino acids (KRTA) at the haemagglutinin (HA) cleavage site enabled trypsin-independent infectivity of this virus. Although maintaining dual receptor-binding preference, its HA antigenicity was distinct from low-pathogenic avian influenza A(H7N9). The neuraminidase substitution R292K conferred a multidrug resistance phenotype.

scholarly journals Treatment of Highly Pathogenic H7N9 Virus-Infected Mice with Baloxavir Marboxil

Viruses ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 1066 ◽  
Author(s):  
Maki Kiso ◽  
Seiya Yamayoshi ◽  
Yuri Furusawa ◽  
Masaki Imai ◽  
Yoshihiro Kawaoka
Keyword(s):  
Virus Infection ◽  
Influenza A ◽  
H7n9 Virus ◽  
Neuraminidase Inhibitors ◽  
Influenza A Viruses ◽  
Lethal Challenge ◽  
Highly Pathogenic ◽  
Limited Efficacy ◽  
H7n9 Influenza ◽  
Influenza H7n9 Virus

Viral neuraminidase inhibitors show limited efficacy in mice infected with H7N9 influenza A viruses isolated from humans. Although baloxavir marboxil protected mice from lethal challenge infection with a low pathogenic avian influenza H7N9 virus isolated from a human, its efficacy in mice infected with a recent highly pathogenic version of H7N9 human isolates is unknown. Here, we examined the efficacy of baloxavir marboxil in mice infected with a highly pathogenic human H7N9 virus, A/Guangdong/17SF003/2016. Treatment of infected mice with a single 1.5 mg/kg dose of baloxavir marboxil protected mice from the highly pathogenic human H7N9 virus infection as effectively as oseltamivir treatment at 50 mg/kg twice a day for five days. Daily treatment for five days at 15 or 50 mg/kg of baloxavir marboxil showed superior therapeutic efficacy, largely preventing virus replication in respiratory organs. These results indicate that baloxavir marboxil is a valuable candidate treatment for human patients suffering from highly pathogenic H7N9 virus infection.

scholarly journals Structural Insight into a Human Neutralizing Antibody against Influenza Virus H7N9

2017 ◽  
Vol 92 (5) ◽  
Author(s):  
Cong Chen ◽  
Liguo Liu ◽  
Yan Xiao ◽  
Sheng Cui ◽  
Jianmin Wang ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Receptor Binding ◽  
Influenza A ◽  
Human Monoclonal Antibody ◽  
H7n9 Virus ◽  
Receptor Binding Site ◽  
Fragment Antigen Binding ◽  
Insight Into

ABSTRACT Since its first emergence in East China in early 2013, many cases of avian influenza A H7N9 have been reported. The disease has extended to 22 provinces in mainland China and some surrounding areas. Strategies to combat viral infection are urgently needed. We previously isolated a human monoclonal antibody, HNIgGA6, that neutralized the H7N9 virus both in vitro and in vivo . In this study, we determined the crystal structure of viral hemagglutinin (HA) globular head bound to the fragment antigen-binding region (Fab) of HNIgGA6. The crystal structure shows that the tip of the HNIgGA6 heavy-chain complementarity-determining region 3 (HCDR3) directly interposes into the receptor binding site (RBS) and mimics, in many respects, the interaction of the sialic acid receptor. Three residues at Y98, H183, and E190, which are critical to human cellular receptor binding, are also essential for HNIgGA6 recognition. Meanwhile, dual mutations at V186G and L226Q in RBS were able to disrupt viral HA1 binding with the antibody. Our study provides a better understanding of the mechanism for protective antibody recognition and a sound foundation for the design of therapeutic drugs and vaccines against H7N9 influenza. IMPORTANCE Neutralization by antibody is one of the most important mechanisms for a host to defend against viral infections. Human-originated antibody HNIgGA6 was generated in response to the natural infectious H7N9 virus and showed potential for use in suppression of H7N9 infection, with possible therapeutic implications. The crystal structure of the HNIgGA6/HA1 complex provided new insight into the protective immune response to H7N9 virus in humans, as well as possibilities for the development of effective H7N9 pandemic vaccines and antiviral molecules.

scholarly journals Human Infection with Highly Pathogenic Avian Influenza A(H7N9) Virus, China

2017 ◽  
Vol 23 (8) ◽  
pp. 1332-1340 ◽  
Author(s):  
Changwen Ke ◽  
Chris Ka Pun Mok ◽  
Wenfei Zhu ◽  
Haibo Zhou ◽  
Jianfeng He ◽  
...  
Keyword(s):  
Avian Influenza ◽  
Influenza A ◽  
Highly Pathogenic Avian Influenza ◽  
Human Infection ◽  
H7n9 Virus ◽  
Highly Pathogenic ◽  
Pathogenic Avian Influenza

scholarly journals Will China’s H7N9 Control Strategy Continue to Be Effective?

2019 ◽  
Vol 6 (6) ◽  
Author(s):  
Guo-Lin Wang ◽  
Gregory C Gray ◽  
Ji-Ming Chen ◽  
Mai-Juan Ma
Keyword(s):  
Virus Infection ◽  
Avian Influenza ◽  
Control Strategy ◽  
Influenza A ◽  
Human Infection ◽  
H7n9 Virus ◽  
Influenza A Viruses ◽  
Highly Pathogenic ◽  
Live Poultry ◽  
Live Poultry Markets

Abstract Since the first outbreak of avian influenza A(H7N9) virus in China in early 2013, several interventions to control the transmission of H7N9 virus from poultry to humans have been implemented. Temporarily closing live poultry markets reduced the risk of human infection to an extent, but it did not prevent the spread of the H7N9 virus among poultry, and this spread eventually led to more human cases. Nevertheless, the mass vaccination of poultry after September 2017 has been highly effective in preventing the H7N9 virus infection in both poultry and humans. In light of the emergence of highly pathogenic H7N9 and H7N2 viruses in unimmunized ducks, vaccination among poultry, especially for ducks, should be accompanied with continued surveillance of H7N9 variants and other avian influenza A viruses that could signal a heightened pandemic risk.

scholarly journals Avian Influenza H7N9 Virus Adaptation to Human Hosts

Viruses ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 871
Author(s):  
Swan Tan ◽  
Muhammad Farhan Sjaugi ◽  
Siew Chinn Fong ◽  
Li Chuin Chong ◽  
Hadia Syahirah Abd Raman ◽  
...  
Keyword(s):  
Amino Acid ◽  
Avian Influenza ◽  
Human Infection ◽  
Amino Acid Substitutions ◽  
Human Adaptation ◽  
H7n9 Virus ◽  
Avian Virus ◽  
Human Viruses ◽  
Virus Adaptation ◽  
Influenza H7n9 Virus

Avian influenza virus A (H7N9), after circulating in avian hosts for decades, was identified as a human pathogen in 2013. Herein, amino acid substitutions possibly essential for human adaptation were identified by comparing the 4706 aligned overlapping nonamer position sequences (1–9, 2–10, etc.) of the reported 2014 and 2017 avian and human H7N9 datasets. The initial set of virus sequences (as of year 2014) exhibited a total of 109 avian-to-human (A2H) signature amino acid substitutions. Each represented the most prevalent substitution at a given avian virus nonamer position that was selectively adapted as the corresponding index (most prevalent sequence) of the human viruses. The majority of these avian substitutions were long-standing in the evolution of H7N9, and only 17 were first detected in 2013 as possibly essential for the initial human adaptation. Strikingly, continued evolution of the avian H7N9 virus has resulted in avian and human protein sequences that are almost identical. This rapid and continued adaptation of the avian H7N9 virus to the human host, with near identity of the avian and human viruses, is associated with increased human infection and a predicted greater risk of human-to-human transmission.

scholarly journals Potent sialic acid inhibitors that target influenza A virus hemagglutinin

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yu-Jen Chang ◽  
Cheng-Yun Yeh ◽  
Ju-Chien Cheng ◽  
Yu-Qi Huang ◽  
Kai-Cheng Hsu ◽  
...  
Keyword(s):  
Sialic Acid ◽  
Antiviral Activity ◽  
Binding Site ◽  
Influenza A Virus ◽  
Receptor Binding ◽  
Influenza A ◽  
The United States ◽  
Ligand Complex ◽  
Receptor Binding Site ◽  
Computational Strategy

AbstractEradicating influenza A virus (IAV) is difficult, due to its genetic drift and reassortment ability. As the infectious cycle is initiated by the influenza glycoprotein, hemagglutinin (HA), which mediates the binding of virions to terminal sialic acids moieties, HA is a tempting target of anti-influenza inhibitors. However, the complexity of the HA structure has prevented delineation of the structural characterization of the HA protein–ligand complex. Our computational strategy efficiently analyzed > 200,000 records of compounds held in the United States National Cancer Institute (NCI) database and identified potential HA inhibitors, by modeling the sialic acid (SA) receptor binding site (RBS) for the HA structure. Our modeling revealed that compound NSC85561 showed significant antiviral activity against the IAV H1N1 strain with EC50 values ranging from 2.31 to 2.53 µM and negligible cytotoxicity (CC50 > 700 µM). Using the NSC85561 compound as the template to generate 12 derivatives, robust bioassay results revealed the strongest antiviral efficacies with NSC47715 and NSC7223. Virtual screening clearly identified three SA receptor binding site inhibitors that were successfully validated in experimental data. Thus, our computational strategy has identified SA receptor binding site inhibitors against HA that show IAV-associated antiviral activity.

scholarly journals Adjuvanted recombinant hemagglutinin H7 vaccine to highly pathogenic influenza A(H7N9) elicits high and sustained antibody responses in healthy adults

npj Vaccines ◽  
2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Christine M. Oshansky ◽  
◽  
James King ◽  
Di Lu ◽  
James Zhou ◽  
...  
Keyword(s):  
Influenza A ◽  
Study Groups ◽  
Cross Reactivity ◽  
Healthy Adults ◽  
Response Strategy ◽  
Seroprotection Rate ◽  
Highly Pathogenic ◽  
Homologous Virus ◽  
Human Infections ◽  
Epidemic Wave

AbstractAn unprecedented number of human infections with avian influenza A(H7N9) in the fifth epidemic wave during the winter of 2016–2017 in China and their antigenic divergence from the viruses that emerged in 2013 prompted development of updated vaccines for pandemic preparedness. We report on the findings of a clinical study in healthy adults designed to evaluate the safety and immunogenicity of three dose levels of recombinant influenza vaccine derived from highly pathogenic A/Guangdong/17SF003/2016 (H7N9) virus adjuvanted with AS03 or MF59 oil-in water emulsions. Most of the six study groups meet the FDA CBER-specified vaccine licensure criterion of 70% seroprotection rate (SPR) for hemagglutination inhibition antibodies to the homologous virus. A substantial proportion of subjects show high cross-reactivity to antigenically distinct heterologous A(H7N9) viruses from the first epidemic wave of 2013. These results provide critical information to develop a pandemic response strategy and support regulatory requirements for vaccination under Emergency Use Authorization.

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