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dc.contributor.authorGagliardi, Talita B
dc.contributor.authorGoldstein, Monty E
dc.contributor.authorSong, Daniel
dc.contributor.authorGray, Kelsey M
dc.contributor.authorJung, Jae W
dc.contributor.authorIgnacio, Maxinne A
dc.contributor.authorStroka, Kimberly M
dc.contributor.authorDuncan, Gregg A
dc.contributor.authorScull, Margaret A
dc.date.accessioned2022-01-31T13:33:16Z
dc.date.available2022-01-31T13:33:16Z
dc.date.issued2022-01-07
dc.identifier.urihttp://hdl.handle.net/10713/17809
dc.description.abstractThe clinical impact of rhinovirus C (RV-C) is well-documented; yet, the viral life cycle remains poorly defined. Thus, we characterized RV-C15 replication at the single-cell level and its impact on the human airway epithelium (HAE) using a physiologically-relevant in vitro model. RV-C15 replication was restricted to ciliated cells where viral RNA levels peaked at 12 hours post-infection (hpi), correlating with elevated titers in the apical compartment at 24hpi. Notably, infection was associated with a loss of polarized expression of the RV-C receptor, cadherin-related family member 3. Visualization of double-stranded RNA (dsRNA) during RV-C15 replication revealed two distinct replication complex arrangements within the cell, likely corresponding to different time points in infection. To further define RVC15 replication sites, we analyzed the expression and colocalization of giantin, phosphatidylinositol- 4-phosphate, and calnexin with dsRNA. Despite observing Golgi fragmentation by immunofluorescence during RV-C15 infection as previously reported for other RVs, a high ratio of calnexin-dsRNA colocalization implicated the endoplasmic reticulum as the primary site for RV-C15 replication in HAE. RV-C15 infection was also associated with elevated stimulator of interferon genes (STING) expression and the induction of incomplete autophagy, a mechanism used by other RVs to facilitate non-lytic release of progeny virions. Notably, genetic depletion of STING in HAE attenuated RV-C15 and -A16 (but not -B14) replication, corroborating a previously proposed proviral role for STING in some RV infections. Finally, RV-C15 infection resulted in a temporary loss in epithelial barrier integrity and the translocation of tight junction proteins while a reduction in mucociliary clearance indicated cytopathic effects on epithelial function. Together, our findings identify both shared and unique features of RV-C replication compared to related rhinoviruses and define the impact of RV-C on both epithelial cell organization and tissue functionality-aspects of infection that may contribute to pathogenesis in vivo. © 2022 Gagliardi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en_US
dc.description.urihttps://doi.org/10.1371/journal.ppat.1010159en_US
dc.language.isoenen_US
dc.publisherPublic Library of Scienceen_US
dc.relation.ispartofPLoS Pathogensen_US
dc.titleRhinovirus C replication is associated with the endoplasmic reticulum and triggers cytopathic effects in an in vitro model of human airway epithelium.en_US
dc.typeArticleen_US
dc.identifier.doi10.1371/journal.ppat.1010159
dc.identifier.pmid34995322
dc.source.journaltitlePLoS pathogens
dc.source.volume18
dc.source.issue1
dc.source.beginpagee1010159
dc.source.endpage
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States


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