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			PubMed Journals: J Virol

  Source:		PMID: 31694947


    		J Virol. 2019 Nov 6. pii: JVI.01363-19. doi:
     		10.1128/JVI.01363-19. [Epub ahead of print]

			Three Amino Acid Changes In Avian
			Coronavirus Spike Protein Allows Binding To
			Kidney Tissue.

			Bouwman KM(1), Parsons LM(2), Berends
			AJ(3), de Vries RP(4), Cipollo JF(2), Verheije
			MH(1).

			Author Information
			(1) Division of Pathology, Department of
			Pathobiology, Faculty of Veterinary Medicine,
			Utrecht University, Utrecht, the Netherlands.
			k.m.bouwman@uu.nl m.h.verheije@uu.nl.
			(2) Center for Biologics Evaluation and
			Research, Food and Drug Administration, Silver
			Spring, Maryland, United States.
			(3) Division of Pathology, Department of
			Pathobiology, Faculty of Veterinary Medicine,
			Utrecht University, Utrecht, the Netherlands.
			(4) Department of Chemical Biology and Drug
			Discovery,
			Utrecht Institute for Pharmaceutical Sciences,
			Utrecht University, Utrecht, The Netherlands.

			Infectious bronchitis virus (IBV) infects ciliated
			epithelial cells in the chicken respiratory tract.
			While some IBV strains replicate locally, others
			can disseminate to various organs, including
			the kidney. Here we elucidate the determinants
			for kidney tropism by studying interactions
			between the receptor binding domain (RBD) of
			the viral attachment protein spike from two IBV
			strains with different tropisms. Recombinantly
			produced RBDs from the nephropathogenic
			IBV strain QX and from the
			non-nephropathogenic strain M41 bound to the
			epithelial cells of the trachea. In contrast, only
			QX-RBD binds more extensively to cells of the
			digestive tract, urogenital tract, and kidneys.
			While removal of sialic acids from tissues
			prevented binding of all proteins to all tissues,
			binding of QX-RBD to trachea and kidney could
			not be blocked by pre-incubation with synthetic
			alpha-2,3-linked sialic acids. The lack of binding
			of QX-RBD to a previously identified IBV-M41
			receptor was confirmed by ELISA,
			demonstrating that tissue binding of QX-RBD is
			dependent on a different sialylated glycan
			receptor. Using chimeric RBD proteins, we
			discovered that the region encompassing
			amino acids 99-159 of QX-RBD was required
			to establish kidney binding. In particular,
			QX-RBD amino acids 110-112 (KIP) were
			sufficient to render IBV-M41 with the ability to
			bind to kidney, while the reciprocal mutations in
			IBV-QX abolished kidney binding completely.
			Structural analysis of both RBDs suggests that
			the receptor binding site for QX is located at a
			different location on the spike than that of
			M41.Importance: Infectious bronchitis virus is
			the causative agent of Infectious bronchitis in
			chickens. Upon infection of chicken flocks, the
			poultry industry faces substantial economic
			losses by diminished egg quality and increased
			morbidity and mortality of infected animals.
			While all IBV strains infect the chicken
			respiratory tract via the ciliated epithelial layer of
			the trachea, some strains can also replicate in
			the kidneys, dividing IBV in two pathotypes:
			non-nephropathogenic (example IBV-M41) and
			nephropathogenic viruses (including IBV-QX).
			Here we set out to identify the determinants for
			the extended nephropathogenic tropism of
			IBV-QX. Our data reveal that each pathotype
			makes use of a different sialylated glycan
			ligand, with binding sites on opposite sides of
			the attachment protein. This knowledge should
			facilitate the design of antivirals to prevent
			coronavirus infections in the field.

			Copyright © 2019 Bouwman et al.

			DOI: 10.1128/JVI.01363-19 PMID: 31694947

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