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Title: Structural Analysis of the Hemagglutinin from the Recent 2013 H7N9 Influenza Virus

Authors:
; ; ; ;  [1]
  1. CDC
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Org.:
OTHER U.S. GOVERNMENTNIGMS
OSTI Identifier:
1258690
Resource Type:
Journal Article
Resource Relation:
Journal Name: Journal of Virology; Journal Volume: 87; Journal Issue: 22
Country of Publication:
United States
Language:
ENGLISH

Citation Formats

Yang, Hua, Carney, Paul J., Chang, Jessie C., Villanueva, Julie M., and Stevens, James. Structural Analysis of the Hemagglutinin from the Recent 2013 H7N9 Influenza Virus. United States: N. p., 2016. Web. doi:10.1128/JVI.01854-13.
Yang, Hua, Carney, Paul J., Chang, Jessie C., Villanueva, Julie M., & Stevens, James. Structural Analysis of the Hemagglutinin from the Recent 2013 H7N9 Influenza Virus. United States. doi:10.1128/JVI.01854-13.
Yang, Hua, Carney, Paul J., Chang, Jessie C., Villanueva, Julie M., and Stevens, James. 2016. "Structural Analysis of the Hemagglutinin from the Recent 2013 H7N9 Influenza Virus". United States. doi:10.1128/JVI.01854-13.
@article{osti_1258690,
title = {Structural Analysis of the Hemagglutinin from the Recent 2013 H7N9 Influenza Virus},
author = {Yang, Hua and Carney, Paul J. and Chang, Jessie C. and Villanueva, Julie M. and Stevens, James},
abstractNote = {},
doi = {10.1128/JVI.01854-13},
journal = {Journal of Virology},
number = 22,
volume = 87,
place = {United States},
year = 2016,
month = 6
}
  • The hemagglutinin (HA) envelope protein of influenza virus mediates viral entry through membrane fusion in the acidic environment of the endosome. Crystal structures of HA in pre- and postfusion states have laid the foundation for proposals for a general fusion mechanism for viral envelope proteins. The large-scale conformational rearrangement of HA at low pH is triggered by a loop-to-helix transition of an interhelical loop (B loop) within the fusion domain and is often referred to as the 'spring-loaded' mechanism. Although the receptor-binding HA1 subunit is believed to act as a 'clamp' to keep the B loop in its metastable prefusionmore » state at neutral pH, the 'pH sensors' that are responsible for the clamp release and the ensuing structural transitions have remained elusive. Here we identify a mutation in the HA2 fusion domain from the influenza virus H2 subtype that stabilizes the HA trimer in a prefusion-like state at and below fusogenic pH. Crystal structures of this putative early intermediate state reveal reorganization of ionic interactions at the HA1-HA2 interface at acidic pH and deformation of the HA1 membrane-distal domain. Along with neutralization of glutamate residues on the B loop, these changes cause a rotation of the B loop and solvent exposure of conserved phenylalanines, which are key residues at the trimer interface of the postfusion structure. Thus, our study reveals the possible initial structural event that leads to release of the B loop from its prefusion conformation, which is aided by unexpected structural changes within the membrane-distal HA1 domain at low pH.« less
  • Influenza A H15 viruses are members of a subgroup (H7-H10-H15) of group 2 hemagglutinin (HA) subtypes that include H7N9 and H10N8 viruses that were isolated from humans during 2013. The isolation of avian H15 viruses is, however, quite rare and, until recently, geographically restricted to wild shorebirds and waterfowl in Australia. The HAs of H15 viruses contain an insertion in the 150-loop (loop beginning at position 150) of the receptor-binding site common to this subgroup and a unique insertion in the 260-loop compared to any other subtype. Here, we show that the H15 HA has a high preference for avianmore » receptor analogs by glycan array analyses. The H15 HA crystal structure reveals that it is structurally closest to H7N9 HA, but the head domain of the H15 trimer is wider than all other HAs due to a tilt and opening of the HA1 subunits of the head domain. The extended 150-loop of the H15 HA retains the conserved conformation as in H7 and H10 HAs. Furthermore, the elongated 260-loop increases the exposed HA surface and can contribute to antigenic variation in H15 HAs. Since avian-origin H15 HA viruses have been shown to cause enhanced disease in mammalian models, further characterization and immune surveillance of H15 viruses are warranted. IMPORTANCEIn the last 2 decades, an apparent increase has been reported for cases of human infection by emerging avian influenza A virus subtypes, including H7N9 and H10N8 viruses isolated during 2013. H15 is the other member of the subgroup of influenza A virus group 2 hemagglutinins (HAs) that also include H7 and H10. H15 viruses have been restricted to Australia, but recent isolation of H15 viruses in western Siberia suggests that they could be spread more globally via the avian flyways that converge and emanate from this region. Here we report on characterization of the three-dimensional structure and receptor specificity of the H15 hemagglutinin, revealing distinct features and specificities that can aid in global surveillance of such viruses for potential spread and emerging threat to the human population.« less
  • The trimeric protein hemagglutinin (HA) of the influenza viral envelope is essential for cell entry. To investigate the interaction of HA with membranes, two 40-residue, cysteine-substituted peptides comprising the loop region and the first part of the coiled-coil stem were synthesized and modified with a nitroxide spin label. Electron paramagnetic resonance analysis revealed that the peptide inserts reversibly into phospholipid vesicles under endosomal pH conditions. This result suggests that some or all of the long coiled-coil trimer of HA may insert into membranes, which could bring the viral and cell membranes closer together and facilitate fusion. 16 refs., 5 figs.