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 avian 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.
Bibliographical noteFunding Information:
This work was funded in part by National Institutes of Health grants R56 AI117675 (to I.A.W.) and R01 AI114730 (to J.C.P.) and a grant from the Kuang Hua Educational Foundation (to J.C.P.). We thank Robyn Stanfield, X. Dai, and M. Elsliger for crystallographic and computational support, Henry Tien of the Robotics Core at the Joint Center for Structural Genomics and Wilson lab for automated crystal screening (supported by NIH grant U54 GM094586), the staffat the Advanced Photon Source beamline 23ID-B (GM/CA CAT). GM/CA CAT is funded in whole or in part with federal funds from the National Cancer Institute (Y1-CO-1020) and NIGMS (Y1-GM-1104). Use of the Advanced Photon Source was supported by the U.S. Department of Energy (DOE), Basic Energy Sciences, Office of Science, under contract DE-AC02-06CH11357. This project was designed by N.T., J.C.P., and I.A.W. X-ray structure determination and analysis were performed by N.T. Glycan array studies were performed by N.T., C.M.N., W.P., and R.M. The manuscript was written by N.T., J.C.P., and I.A.W.
© 2017 American Society for Microbiology. All Rights Reserved.
- Glycan arrays
- H15 subtype
- Influenza virus
- Receptor binding
- X-ray crystallography