title: Human coronavirus 229E infects polarized airway epithelia from the apical surface.
abstract: Gene transfer to differentiated airway epithelia with existing viral vectors is very inefficient when they are applied to the apical surface. This largely reflects the polarized distribution of receptors on the basolateral surface. To identify new receptor-ligand interactions that might be used to redirect vectors to the apical surface, we investigated the process of infection of airway epithelial cells by human coronavirus 229E (HCoV-229E), a common cause of respiratory tract infections. Using immunohistochemistry, we found the receptor for HCoV-229E (CD13 or aminopeptidase N) localized mainly to the apical surface of airway epithelia. When HCoV-229E was applied to the apical or basolateral surface of well-differentiated primary cultures of human airway epithelia, infection primarily occurred from the apical side. Similar results were noted when the virus was applied to cultured human tracheal explants. Newly synthesized virions were released mainly to the apical side. Thus, HCoV-229E preferentially infects human airway epithelia from the apical surface. The spike glycoprotein that mediates HCoV-229E binding and fusion to CD13 is a candidate for pseudotyping retroviral envelopes or modifying other viral vectors.
authors.affiliation: Program in Gene Therapy, Department of Pediatrics, University of Iowa College of Medicine, Iowa City, Iowa 52242, USA.
authors.forename: G
authors.initials: G
authors.lastname: Wang
authors.forename: C
authors.initials: C
authors.lastname: Deering
authors.forename: M
authors.initials: M
authors.lastname: Macke
authors.forename: J
authors.initials: J
authors.lastname: Shao
authors.forename: R
authors.initials: R
authors.lastname: Burns
authors.forename: D M
authors.initials: DM
authors.lastname: Blau
authors.forename: K V
authors.initials: KV
authors.lastname: Holmes
authors.forename: B L
authors.initials: BL
authors.lastname: Davidson
authors.forename: S
authors.initials: S
authors.lastname: Perlman
authors.forename: P B
authors.initials: PB
authors.lastname: McCray
mesh_terms: D002460:Cell Line; D016764:Cell Polarity; D017934:Coronavirus / Q000502:physiology*; D028941:Coronavirus 229E, Human; D018352:Coronavirus Infections / Q000473:pathology / Q000821:virology*; D004847:Epithelial Cells / Q000473:pathology / Q000821:virology*; D006801:Humans; D014132:Trachea / Q000821:virology*; D014779:Virus Replication