Human Coronavirus HKU1 Spike Protein Uses O-Acetylated Sialic Acid as an Attachment Receptor Determinant and Employs Hemagglutinin-Esterase Protein as a Receptor-Destroying Enzyme

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  • Xingchuan Huang
    • Other Affiliation: National Institute of Biological Sciences, Changping, Beijing, China
  • Wenjuan Dong
    • Other Affiliation: National Institute of Biological Sciences, Changping, Beijing, China
  • Aleksandra Milewska
    • Other Affiliation: Microbiology Department, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland
  • Anna Golda
    • Other Affiliation: Microbiology Department, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland
  • Yonghe Qi
    • Other Affiliation: National Institute of Biological Sciences, Changping, Beijing, China ; Beijing Normal University Graduate Program, National Institute of Biological Sciences, Beijing, China
  • Quan K. Zhu
    • Other Affiliation: Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, and Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA
  • Wayne A. Marasco
    • Other Affiliation: Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, and Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA
  • Ralph S. Baric
    • Other Affiliation: Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, North Carolina, USA ; Department of Epidemiology, University of North Carolina, Chapel Hill, North Carolina, USA
  • Amy C. Sims
    • Other Affiliation: Department of Epidemiology, University of North Carolina, Chapel Hill, North Carolina, USA
  • Krzysztof Pyrc
    • Other Affiliation: Microbiology Department, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland ; Malopolska Centre of Biotechnology, Jagiellonian University, Krakow, Poland
  • Wenhui Li
    • Other Affiliation: National Institute of Biological Sciences, Changping, Beijing, China
  • Jianhua Sui
    • Other Affiliation: National Institute of Biological Sciences, Changping, Beijing, China ; China Agricultural University Graduate Program, National Institute of Biological Sciences, Beijing, China
Abstract
  • ABSTRACT Human coronavirus (hCoV) HKU1 is one of six hCoVs identified to date and the only one with an unidentified cellular receptor. hCoV-HKU1 encodes a hemagglutinin-esterase (HE) protein that is unique to the group a betacoronaviruses (group 2a). The function of HKU1-HE remains largely undetermined. In this study, we examined binding of the S1 domain of hCoV-HKU1 spike to a panel of cells and found that the S1 could specifically bind on the cell surface of a human rhabdomyosarcoma cell line, RD. Pretreatment of RD cells with neuraminidase (NA) and trypsin greatly reduced the binding, suggesting that the binding was mediated by sialic acids on glycoproteins. However, unlike other group 2a CoVs, e.g., hCoV-OC43, for which 9- O -acetylated sialic acid (9- O -Ac-Sia) serves as a receptor determinant, HKU1-S1 bound with neither 9- O -Ac-Sia-containing glycoprotein(s) nor rat and mouse erythrocytes. Nonetheless, the HKU1-HE was similar to OC43-HE, also possessed sialate- O -acetylesterase activity, and acted as a receptor-destroying enzyme (RDE) capable of eliminating the binding of HKU1-S1 to RD cells, whereas the O -acetylesterase-inactive HKU1-HE mutant lost this capacity. Using primary human ciliated airway epithelial (HAE) cell cultures, the only in vitro replication model for hCoV-HKU1 infection, we confirmed that pretreatment of HAE cells with HE but not the enzymatically inactive mutant blocked hCoV-HKU1 infection. These results demonstrate that hCoV-HKU1 exploits O -Ac-Sia as a cellular attachment receptor determinant to initiate the infection of host cells and that its HE protein possesses the corresponding sialate- O -acetylesterase RDE activity. IMPORTANCE Human coronaviruses (hCoV) are important human respiratory pathogens. Among the six hCoVs identified to date, only hCoV-HKU1 has no defined cellular receptor. It is also unclear whether hemagglutinin-esterase (HE) protein plays a role in viral entry. In this study, we found that, similarly to other members of the group 2a CoVs, sialic acid moieties on glycoproteins are critical receptor determinants for the hCoV-HKU1 infection. Interestingly, the virus seems to employ a type of sialic acid different from those employed by other group 2a CoVs. In addition, we determined that the HKU1-HE protein is an O -acetylesterase and acts as a receptor-destroying enzyme (RDE) for hCoV-HKU1. This is the first study to demonstrate that hCoV-HKU1 uses certain types of O -acetylated sialic acid residues on glycoproteins to initiate the infection of host cells and that the HKU1-HE protein possesses sialate- O -acetylesterase RDE activity.
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  • Article
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  • In Copyright
Journal title
  • Journal of Virology
Journal volume
  • 89
Journal issue
  • 14
Page start
  • 7202
Page end
  • 7213
Language
  • English
ISSN
  • 1098-5514
  • 0022-538X
  • 1070-6321
Publisher
  • American Society for Microbiology

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