title: Novel Receptor Specificity of Avian Gammacoronaviruses That Cause Enteritis.
abstract: Viruses exploit molecules on the target membrane as receptors for attachment and entry into host cells. Thus, receptor expression patterns can define viral tissue tropism and might to some extent predict the susceptibility of a host to a particular virus. Previously, others and we have shown that respiratory pathogens of the genus Gammacoronavirus, including chicken infectious bronchitis virus (IBV), require specific α2,3-linked sialylated glycans for attachment and entry. Here, we studied determinants of binding of enterotropic avian gammacoronaviruses, including turkey coronavirus (TCoV), guineafowl coronavirus (GfCoV), and quail coronavirus (QCoV), which are evolutionarily distant from respiratory avian coronaviruses based on the viral attachment protein spike (S1). We profiled the binding of recombinantly expressed S1 proteins of TCoV, GfCoV, and QCoV to tissues of their respective hosts. Protein histochemistry showed that the tissue binding specificity of S1 proteins of turkey, quail, and guineafowl CoVs was limited to intestinal tissues of each particular host, in accordance with the reported pathogenicity of these viruses in vivo. Glycan array analyses revealed that, in contrast to the S1 protein of IBV, S1 proteins of enteric gammacoronaviruses recognize a unique set of nonsialylated type 2 poly-N-acetyl-lactosamines. Lectin histochemistry as well as tissue binding patterns of TCoV S1 further indicated that these complex N-glycans are prominently expressed on the intestinal tract of various avian species. In conclusion, our data demonstrate not only that enteric gammacoronaviruses recognize a novel glycan receptor but also that enterotropism may be correlated with the high specificity of spike proteins for such glycans expressed in the intestines of the avian host.
  
  
  OBJECTIVE
  Avian coronaviruses are economically important viruses for the poultry industry. While infectious bronchitis virus (IBV), a respiratory pathogen of chickens, is rather well known, other viruses of the genus Gammacoronavirus, including those causing enteric disease, are hardly studied. In turkey, guineafowl, and quail, coronaviruses have been reported to be the major causative agent of enteric diseases. Specifically, turkey coronavirus outbreaks have been reported in North America, Europe, and Australia for several decades. Recently, a gammacoronavirus was isolated from guineafowl with fulminating disease. To date, it is not clear why these avian coronaviruses are enteropathogenic, whereas other closely related avian coronaviruses like IBV cause respiratory disease. A comprehensive understanding of the tropism and pathogenicity of these viruses explained by their receptor specificity and receptor expression on tissues was therefore needed. Here, we identify a novel glycan receptor for enteric avian coronaviruses, which will further support the development of vaccines.
authors.affiliation: Department of Pathobiology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
authors.forename: I N
authors.initials: IN
authors.lastname: Ambepitiya Wickramasinghe
authors.affiliation: Departments of Cell and Molecular Biology, Chemical Physiology, and Immunology and Microbial Science, The Scripps Research Institute, La Jolla, California, USA.
authors.forename: R P
authors.initials: RP
authors.lastname: de Vries
authors.affiliation: Department of Pathobiology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
authors.forename: E A W S
authors.initials: EA
authors.lastname: Weerts
authors.affiliation: Department of Pathobiology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
authors.forename: S J
authors.initials: SJ
authors.lastname: van Beurden
authors.affiliation: Departments of Cell and Molecular Biology, Chemical Physiology, and Immunology and Microbial Science, The Scripps Research Institute, La Jolla, California, USA.
authors.forename: W
authors.initials: W
authors.lastname: Peng
authors.affiliation: Departments of Cell and Molecular Biology, Chemical Physiology, and Immunology and Microbial Science, The Scripps Research Institute, La Jolla, California, USA.
authors.forename: R
authors.initials: R
authors.lastname: McBride
authors.affiliation: INRA and Université de Toulouse, INP, ENVT, UMR 1225 IHAP, Toulouse, France.
authors.forename: M
authors.initials: M
authors.lastname: Ducatez
authors.affiliation: College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina, USA.
authors.forename: J
authors.initials: J
authors.lastname: Guy
authors.affiliation: Université Européenne de Bretagne, Agence Nationale de Sécurité Sanitaire, Unité de Virologie Immunologie et Parasitologie Aviaires et Cunicoles, Ploufragan, France.
authors.forename: P
authors.initials: P
authors.lastname: Brown
authors.affiliation: Université Européenne de Bretagne, Agence Nationale de Sécurité Sanitaire, Unité de Virologie Immunologie et Parasitologie Aviaires et Cunicoles, Ploufragan, France.
authors.forename: N
authors.initials: N
authors.lastname: Eterradossi
authors.affiliation: Department of Pathobiology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
authors.forename: A
authors.initials: A
authors.lastname: Gröne
authors.affiliation: Departments of Cell and Molecular Biology, Chemical Physiology, and Immunology and Microbial Science, The Scripps Research Institute, La Jolla, California, USA.
authors.forename: J C
authors.initials: JC
authors.lastname: Paulson
authors.affiliation: Department of Pathobiology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands m.h.verheije@uu.nl.
authors.forename: M H
authors.initials: MH
authors.lastname: Verheije
mesh_terms: D000818:Animals; D002645:Chickens / Q000821:virology; D018352:Coronavirus Infections / Q000662:veterinary* / Q000821:virology; D004752:Coronavirus, Turkey / Q000378:metabolism*; D004751:Enteritis / Q000821:virology; D005685:Galactans / Q000378:metabolism; D001351:Infectious bronchitis virus / Q000378:metabolism; D007422:Intestines / Q000821:virology; D011201:Poultry Diseases / Q000821:virology; D011485:Protein Binding / Q000235:genetics; D011991:Receptors, Virus / Q000378:metabolism*; D014422:Turkeys / Q000821:virology; D056189:Viral Tropism / Q000235:genetics*
chemical_list: D005685:Galactans; D011991:Receptors, Virus; C023041:poly-N-acetylgalactosamine