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Clathrin adaptor AP1B controls adenovirus infectivity of epithelial cells.

TitleClathrin adaptor AP1B controls adenovirus infectivity of epithelial cells.
Publication TypeJournal Article
Year of Publication2009
AuthorsDiaz F, Gravotta D, Deora A, Schreiner R, Schoggins J, Falck-Pedersen E, Rodriguez-Boulan E
JournalProc Natl Acad Sci U S A
Volume106
Issue27
Pagination11143-8
Date Published2009 Jul 07
ISSN1091-6490
KeywordsAdaptor Protein Complex beta Subunits, Adenoviridae, Animals, Cell Line, Cell Polarity, Clathrin, Coxsackie and Adenovirus Receptor-Like Membrane Protein, Dogs, Endocytosis, Epithelial Cells, Gene Knockdown Techniques, Humans, Protein Transport, Receptors, Virus, Retinal Pigment Epithelium, Tight Junctions
Abstract

Adenoviruses invading the organism via normal digestive or respiratory routes require the Coxsackie-adenovirus receptor (CAR) to infect the epithelial barrier cells. Because CAR is a component of tight junctions and the basolateral membrane and is normally excluded from the apical membrane, most epithelia are resistant to adenoviruses. However, we discovered that a specialized epithelium, the retinal pigment epithelium (RPE), anomalously expressed CAR at the apical surface and was highly susceptible to adenovirus infection. These properties of RPE cells correlated with the absence of the epithelial-specific clathrin adaptor AP1B. Furthermore, knockdown of this basolateral sorting adaptor in adenovirus-resistant MDCK cells promoted apical localization of CAR and increased dramatically Adenovirus infectivity. Targeting assays showed that AP1B is required for accurate basolateral recycling of CAR after internalization. AP1B knock down MDCK cells missorted CAR from recycling endosomes to the apical surface. In summary, we have characterized the cellular machinery responsible for normal sorting of an adenovirus receptor and illustrated how tissue-specific variations in such machinery result in drastic changes in tissue-susceptibility to adenoviruses.

DOI10.1073/pnas.0811227106
Alternate JournalProc Natl Acad Sci U S A
PubMed ID19549835
PubMed Central IDPMC2708682
Grant ListR01 EY008538 / EY / NEI NIH HHS / United States
R01 GM034107 / GM / NIGMS NIH HHS / United States
EY08538 / EY / NEI NIH HHS / United States
GM34107 / GM / NIGMS NIH HHS / United States

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