Adenovirus entry from the apical surface of polarized epithelia is facilitated by the host innate immune response

PLoS Pathogens
Poornima L N KothaKatherine Julie Diane Ashbourne Excoffon

Abstract

Prevention of viral-induced respiratory disease begins with an understanding of the factors that increase or decrease susceptibility to viral infection. The primary receptor for most adenoviruses is the coxsackievirus and adenovirus receptor (CAR), a cell-cell adhesion protein normally localized at the basolateral surface of polarized epithelia and involved in neutrophil transepithelial migration. Recently, an alternate isoform of CAR, CAREx8, has been identified at the apical surface of polarized airway epithelia and is implicated in viral infection from the apical surface. We hypothesized that the endogenous role of CAREx8 may be to facilitate host innate immunity. We show that IL-8, a proinflammatory cytokine and a neutrophil chemoattractant, stimulates the protein expression and apical localization of CAREx8 via activation of AKT/S6K and inhibition of GSK3β. Apical CAREx8 tethers infiltrating neutrophils at the apical surface of a polarized epithelium. Moreover, neutrophils present on the apical-epithelial surface enhance adenovirus entry into the epithelium. These findings suggest that adenovirus evolved to co-opt an innate immune response pathway that stimulates the expression of its primary receptor, apical CAREx8, to al...Continue Reading

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Citations

Sep 26, 2015·Viruses·Jesús M Torres-Flores, Carlos F Arias
Jan 4, 2017·Virology·Priyanka SharmaKatherine J D A Excoffon
Jul 1, 2017·Journal of Virology·Zekun WangJianming Qiu
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Jun 2, 2020·Journal of Medical Virology·Xuefeng Liu, Abdul M Mondal
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Sep 14, 2018·Frontiers in Cellular and Infection Microbiology·Eveliina KarelehtoKatja C Wolthers
Jun 17, 2020·FEBS Letters·Urs F Greber
Jul 25, 2019·International Journal of Molecular Sciences·Jeanne K DuShane, Melissa S Maginnis
Jul 14, 2016·Pediatric Pulmonology·Elena C CavallaroDani-Louise Dixon
Feb 27, 2021·Tissue Barriers·Debra T LinfieldFariba Rezaee

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Methods Mentioned

BETA
PCR
fluorescence microscopy
transfection

Software Mentioned

Excel
Metamorph Meta Imaging
SPSS
Metamorph
Graph Pad Prism

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