The Coxsackievirus and Adenovirus Receptor Has a Short Half-Life in Epithelial Cells.

Poornima Kotha Lakshmi Narayan,Abimbola O Kolawole,James M Readler,Mahmoud S Alghamri,Ran Yan,Katherine J D A Excoffon,Vladislav Snitsarev,Trisha L Brockman,Priyanka Sharma

doi:10.3390/pathogens11020173

Poornima Kotha Lakshmi Narayan, Abimbola O Kolawole + Show 7 more

Open Access

https://doi.org/10.3390/pathogens11020173

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Abstract

The coxsackievirus and adenovirus receptor (CAR) is an essential cellular protein that is involved in cell adhesion, cell signaling, and viral infection. The 8-exon encoded isoform (CAREx8) resides at the apical surface of polarized epithelia, where it is accessible as a receptor for adenovirus entering the airway lumen. Given its pivotal role in viral infection, it is a target for antiviral strategies. To understand the regulation of CAREx8 and determine the feasibility of receptor downregulation, the half-life of total and apical localized CAREx8 was determined and correlated with adenovirus transduction. Total and apical CAREx8 has a relatively short half-life of approximately 2 h. The half-life of apical CAREx8 correlates well with adenovirus transduction. These results suggest that antiviral strategies that aim to degrade the primary receptor for apical adenovirus infection will be effective within a relatively short time frame after application.

Highlights

Acute respiratory tract infections are a major cause of morbidity and mortality worldwide, especially among children and elderly populations
Two transmembrane isoforms of coxsackievirus and adenovirus receptor (CAR) are present in polarized epithelial cells: an isoform encoded by the first seven exons (CAREx7) of the CXADR gene and an isoform that is alternatively spliced from a cryptic splice site within the seventh exon to the eighth exon (CAREx8) [8,9]
CAREx7, the more abundant isoform, localizes at the basolateral surface of polarized epithelial cells, while CAREx8 localizes at the apical surface

Summary

Introduction

Acute respiratory tract infections are a major cause of morbidity and mortality worldwide, especially among children and elderly populations. Our lab has previously shown that CAREx8 mediates apical adenoviral infection in polarized epithelial cells and that the susceptibility to adenovirus infection correlates with the level of CAREx8 expression [8,10,11,12,13,14]. HAdV appears to have co-opted an innate immune response that stimulates the expression and the localization of CAREx8 at the apical surface of polarized epithelial cells in order to more efficiently gain entry and initiate infection [13].

Results

Conclusion