Human coronavirus 229E infects polarized airway epithelia from the apical surface

Gene transfer to differentiated airway epithelia with existing viral vector s is very inefficient when they are applied to the apical surface. This lar gely reflects the polarized distribution of receptors on the basolateral su rface. To identify new receptor-ligand interactions that might be used to r edirect vectors to the apical surface, we investigated the process of infec tion of airway epithelial cells by human coronavirus 2293 (HCoV-229E), a co mmon cause of respiratory tract infections. Using immunohistochemistry, we found the receptor for HCoV-229E (CD13 or aminopeptidase N) localized mainl y to the apical surface of airway epithelia, When HCoV-229E was applied to the apical or basolateral surface of well-differentiated primary cultures o f human airway epithelia, infection primarily occurred from the epical side . Similar results were noted when the virus was applied to cultured human t racheal explants. Newly synthesized virions were released mainly to the api cal side. Thus, HCoV-229E preferentially infects human airway epithelia fro m the apical surface. The spike glycoprotein that mediates HCoV-229E bindin g and fusion to CD13 is a candidate for pseudotyping retroviral envelopes o r modifying other viral vectors.