title: Measles virus preferentially transduces the basolateral surface of well-differentiated human airway epithelia.
abstract: Measles virus (MV) is typically spread by aerosol droplets and enters via the respiratory tract. The progression of MV infection has been widely studied; yet, the pathway for virus entry in polarized human airway epithelia has not been investigated. Herein we report the use of a replication-competent Edmonston vaccine strain of MV expressing enhanced green fluorescent protein (MV-eGFP) to infect primary cultures of well-differentiated human airway epithelia. Previous studies with polarized Caco-2 cells (intestine-derived human epithelia) and MDCK cells (kidney-derived canine epithelia) demonstrated that MV primarily infected and exited the apical surface. In striking contrast, our results indicate that MV preferentially transduces human airway cells from the basolateral surface; however, virus release remains in an apical direction. When MV-eGFP was applied apically or basolaterally to primary cultures of airway epithelia, discrete foci of eGFP expression appeared and grew; however, the cell layer integrity was maintained for the duration of the study (7 days). Interestingly, utilizing immunohistochemistry and confocal microscopy, we observed widespread expression of the receptor for the vaccine strain of MV (CD46) at greatest abundance on the apical surface of the differentiated human airway epithelia as well as in human tracheal tissue sections. These data suggest that the progression of MV infection through the respiratory epithelium may involve pathways other than direct binding and entry through the apical surface of airway epithelia.
authors.affiliation: Department of Pediatrics, Program in Gene Therapy, The University of Iowa College of Medicine, Iowa City, IA 52242, USA.
authors.forename: Patrick L
authors.initials: PL
authors.lastname: Sinn
authors.forename: Greg
authors.initials: G
authors.lastname: Williams
authors.forename: Sompong
authors.initials: S
authors.lastname: Vongpunsawad
authors.forename: Roberto
authors.initials: R
authors.lastname: Cattaneo
authors.forename: Paul B
authors.initials: PB
authors.lastname: McCray
mesh_terms: D015703:Antigens, CD / Q000378:metabolism; D001980:Bronchi / Q000166:cytology / Q000821:virology*; D018938:Caco-2 Cells; D002454:Cell Differentiation; D016764:Cell Polarity; D002478:Cells, Cultured; D004848:Epithelium / Q000821:virology*; D006801:Humans; D007150:Immunohistochemistry; D008457:Measles / Q000821:virology*; D008459:Measles virus / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins / Q000378:metabolism; D018613:Microscopy, Confocal; D011991:Receptors, Virus / Q000378:metabolism; D014161:Transduction, Genetic; D014779:Virus Replication
chemical_list: D015703:Antigens, CD; C497857:CD46 protein, human; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins; D011991:Receptors, Virus