Receptor binding by H10 influenza viruses

Vachieri, S.G.; Xiong, Xiaoli; Collins, Patrick J.; Walker, P.A.; Martin, Stephen R.; Haire, L.F.; Zhang, Ying; McCauley, John W.; Gamblin, S.J.; Skehel, J.J.

doi:10.1038/nature13443

Cited by 72 publications

(98 citation statements)

References 25 publications

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“…All the H10 chicken viruses and the human isolate had an HA Q220R substitution (residue 210, H3 numbering) relative to the duck viruses. This residue is located in the trimer interface of the HA protein (28). This substitution was shown to increase the pH of virus fusion and viral replication of an H3N2 virus in murine tracheal epithelial cells and lungs of mice (29).…”

Section: Resultsmentioning

confidence: 99%

Emergence and Evolution of H10 Subtype Influenza Viruses in Poultry in China

Lam

Chai

et al. 2015

J Virol

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The cases of human infections with H10N8 viruses identified in late 2013 and early 2014 in Jiangxi, China, have raised concerns over the origin, prevalence, and development of these viruses in this region. Our long-term influenza surveillance of poultry and migratory birds in southern China in the past 12 years showed that H10 influenza viruses have been introduced from migratory to domestic ducks over several winter seasons at sentinel duck farms at Poyang Lake, where domestic ducks share their water body with overwintering migratory birds. H10 viruses were never detected in terrestrial poultry in our survey areas until August 2013, when they were identified at live-poultry markets in Jiangxi. Since then, we have isolated 124 H10N8 or H10N6 viruses from chickens at local markets, revealing an ongoing outbreak. Phylogenetic analysis of H10 and related viruses showed that the chicken H10N8 viruses were generated through multiple reassortments between H10 and N8 viruses from domestic ducks and the enzootic chicken H9N2 viruses. These chicken reassortant viruses were highly similar to the human isolate, indicating that market chickens were the source of human infection. Recently, the H10 viruses further reassorted, apparently with H5N6 viruses, and generated an H10N6 variant. The emergence and prevalence of H10 viruses in chickens and the occurrence of human infections provide direct evidence of the threat from the current influenza ecosystem in China. IMPORTANCEAfter the outbreak of avian-origin H7N9 influenza viruses in China, fatal human infections with a novel H10N8 virus were reported. Utilizing data from 12 years of influenza surveillance in southern China, we showed that H10 viruses were regularly introduced by migratory ducks to domestic ducks on Poyang Lake, a major aggregative site of migratory birds in Asia. The H10 viruses were maintained and amplified in domestic ducks and then transmitted to chickens and reassorted with enzootic H9N2 viruses, leading to an outbreak and human infections at live-poultry markets. The emergence of the H10N8 virus, following a pathway similar to that of the recent H7N9 virus, highlights the role of domestic ducks and the current influenza ecosystem in China that facilitates influenza viruses moving from their reservoir hosts through the live-poultry system to cause severe consequences for public health.

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Section: Resultsmentioning

confidence: 99%

Emergence and Evolution of H10 Subtype Influenza Viruses in Poultry in China

Lam

Chai

et al. 2015

J Virol

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“…However, surveillance should be emphasized for H10N8 in the event that it acquires new mutations in HA protein as seen for H7N9 between Shanghai-1 and Anhui-1. Recently, Skehel and colleagues 33 examined the receptorbinding properties of an avian H10N2 virus, revealing that the avian H10 virus possesses high avidity for human receptors. The lower avidities observed in our work might reflect the different methods used (for example, under different temperature settings).…”

Section: Discussionmentioning

confidence: 99%

“…In their avian H10/human receptor analogue complex structure, they observed that the residue Q222 of the 220 loop forms a strong hydrogen bond with the human receptor, which is used to explain the phenomenon that avian H10 virus has high avidity for human receptors. Then, based on the similarity of residues in the receptor-binding site of HAs between the avian H10 virus and human-infecting H10 virus, Vachieri et al 33 concluded that the human-infecting H10 virus should possess a high avidity for human receptors. In their humaninfecting H10/human receptor analogue complex structure, they observed that residue R137 forms a 'potential' hydrogen bond with the human receptor, which is helpful for human receptor binding 33 .…”

Section: Discussionmentioning

confidence: 99%

“…Then, based on the similarity of residues in the receptor-binding site of HAs between the avian H10 virus and human-infecting H10 virus, Vachieri et al 33 concluded that the human-infecting H10 virus should possess a high avidity for human receptors. In their humaninfecting H10/human receptor analogue complex structure, they observed that residue R137 forms a 'potential' hydrogen bond with the human receptor, which is helpful for human receptor binding 33 . Note that in avian H10, the residue at position 137 is a lysine (K), which points away from the receptor-binding site and has no hydrogen bond interaction with the human receptor, leading to a minimal impact on the 220-loop residues including Q222.…”

Section: Discussionmentioning

confidence: 99%

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Structural basis for preferential avian receptor binding by the human-infecting H10N8 avian influenza virus

Wang

Zhang

et al. 2015

Nat Commun

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Since December 2013, at least three cases of human infections with H10N8 avian influenza virus have been reported in China, two of them being fatal. To investigate the epidemic potential of H10N8 viruses, we examined the receptor binding property of the first human isolate, A/Jiangxi-Donghu/346/2013 (JD-H10N8), and determined the structures of its haemagglutinin (HA) in complex with both avian and human receptor analogues. Our results suggest that JD-H10N8 preferentially binds the avian receptor and that residue R137-localized within the receptor-binding site of HA-plays a key role in this preferential binding. Compared with the H7N9 avian influenza viruses, JD-H10N8 did not exhibit the enhanced binding to human receptors observed with the prevalent H7N9 virus isolate Anhui-1, but resembled the receptor binding activity of the early-outbreak H7N9 isolate (Shanghai-1). We conclude that the H10N8 virus is a typical avian influenza virus.

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“…Furthermore, an avian H10N7 strain was found to be the etiological agent responsible for the massive die-off harbor seals in the Baltic Sea, an epidemic that killed more than 10% of the local seal population (4)(5)(6). The receptor binding profile of H10 viruses is currently debated (7)(8)(9)(10)(11)(12), but the subtype has been proven to cause productive infections in humans (13,14). Currently, the only treatment option for patients infected with an H10 subtype influenza virus is the use of antiviral inhibitors that target the viral neuraminidase (NA).…”

mentioning

confidence: 99%

Hemagglutinin Stalk- and Neuraminidase-Specific Monoclonal Antibodies Protect against Lethal H10N8 Influenza Virus Infection in Mice

Wohlbold

Chromikova

Tan

et al. 2016

J Virol

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Between November 2013 and February 2014, China reported three human cases of H10N8 influenza virus infection in the Jiangxi province, two of which were fatal. Using hybridoma technology, we isolated a panel of H10-and N8-directed monoclonal antibodies (MAbs) and further characterized the binding reactivity of these antibodies (via enzyme-linked immunosorbent assay) to a range of purified virus and recombinant protein substrates. The H10-directed MAbs displayed functional hemagglutination inhibition (HI) and neutralization activity, and the N8-directed antibodies displayed functional neuraminidase inhibition (NI) activity against H10N8. Surprisingly, the HI-reactive H10 antibodies, as well as a previously generated, group 2 hemagglutinin (HA) stalk-reactive antibody, demonstrated NI activity against H10N8 and an H10N7 strain; this phenomenon was absent when virus was treated with detergent, suggesting the anti-HA antibodies inhibited neuraminidase enzymatic activity through steric hindrance. We tested the prophylactic efficacy of one representative H10-reactive, N8-reactive, and group 2 HA stalk-reactive antibody in vivo using a BALB/c challenge model. All three antibodies were protective at a high dose (5 mg/kg). At a low dose (0.5 mg/kg), only the anti-N8 antibody prevented weight loss. Together, these data suggest that antibody targets other than the globular head domain of the HA may be efficacious in preventing influenza virus-induced morbidity and mortality. IMPORTANCEAvian H10N8 and H10N7 viruses have recently crossed the species barrier, causing morbidity and mortality in humans and other mammals. Although these reports are likely isolated incidents, it is possible that more cases may emerge in future winter seasons, similar to H7N9. Furthermore, regular transmission of avian influenza viruses to humans increases the risk of adaptive mutations and reassortment events, which may result in a novel virus with pandemic potential. Currently, no specific therapeutics or vaccines are available against the H10N8 influenza virus subtype. We generated a panel of H10-and N8-reactive MAbs. Although these antibodies may practically be developed into therapeutic agents, characterizing the protective potential of MAbs that have targets other than the HA globular head domain will provide insight into novel antibody-mediated mechanisms of protection and help to better understand correlates of protection for influenza A virus infection. R ecently, avian influenza A viruses of the H10 subtype have been reported to infect seals and humans and have generated concern over their pandemic potential. Three human cases of H10N8 virus have been reported in China so far, two of which were fatal (1-3). Furthermore, an avian H10N7 strain was found to be the etiological agent responsible for the massive die-off harbor seals in the Baltic Sea, an epidemic that killed more than 10% of the local seal population (4-6). The receptor binding profile of H10 viruses is currently debated (7-12), but the subtype has been proven to cause ...

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Receptor binding by H10 influenza viruses

Cited by 72 publications

References 25 publications

Emergence and Evolution of H10 Subtype Influenza Viruses in Poultry in China

Emergence and Evolution of H10 Subtype Influenza Viruses in Poultry in China

Structural basis for preferential avian receptor binding by the human-infecting H10N8 avian influenza virus

Hemagglutinin Stalk- and Neuraminidase-Specific Monoclonal Antibodies Protect against Lethal H10N8 Influenza Virus Infection in Mice

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