In:
PLOS Pathogens, Public Library of Science (PLoS), Vol. 18, No. 1 ( 2022-1-7), p. e1010159-
Kurzfassung:
The 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 RV-C15 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 .
Materialart:
Online-Ressource
ISSN:
1553-7374
DOI:
10.1371/journal.ppat.1010159
DOI:
10.1371/journal.ppat.1010159.g001
DOI:
10.1371/journal.ppat.1010159.g002
DOI:
10.1371/journal.ppat.1010159.g003
DOI:
10.1371/journal.ppat.1010159.g004
DOI:
10.1371/journal.ppat.1010159.g005
DOI:
10.1371/journal.ppat.1010159.g006
DOI:
10.1371/journal.ppat.1010159.g007
DOI:
10.1371/journal.ppat.1010159.t001
DOI:
10.1371/journal.ppat.1010159.t002
DOI:
10.1371/journal.ppat.1010159.t003
DOI:
10.1371/journal.ppat.1010159.s001
DOI:
10.1371/journal.ppat.1010159.s002
DOI:
10.1371/journal.ppat.1010159.s003
DOI:
10.1371/journal.ppat.1010159.s004
DOI:
10.1371/journal.ppat.1010159.s005
DOI:
10.1371/journal.ppat.1010159.s006
DOI:
10.1371/journal.ppat.1010159.s007
DOI:
10.1371/journal.ppat.1010159.s008
DOI:
10.1371/journal.ppat.1010159.s009
DOI:
10.1371/journal.ppat.1010159.s010
DOI:
10.1371/journal.ppat.1010159.s011
DOI:
10.1371/journal.ppat.1010159.s012
DOI:
10.1371/journal.ppat.1010159.s013
DOI:
10.1371/journal.ppat.1010159.s014
DOI:
10.1371/journal.ppat.1010159.s015
DOI:
10.1371/journal.ppat.1010159.s016
DOI:
10.1371/journal.ppat.1010159.s017
DOI:
10.1371/journal.ppat.1010159.s018
DOI:
10.1371/journal.ppat.1010159.s019
DOI:
10.1371/journal.ppat.1010159.s020
DOI:
10.1371/journal.ppat.1010159.s021
DOI:
10.1371/journal.ppat.1010159.s022
DOI:
10.1371/journal.ppat.1010159.s023
DOI:
10.1371/journal.ppat.1010159.s024
DOI:
10.1371/journal.ppat.1010159.s025
DOI:
10.1371/journal.ppat.1010159.s026
DOI:
10.1371/journal.ppat.1010159.s027
Sprache:
Englisch
Verlag:
Public Library of Science (PLoS)
Publikationsdatum:
2022
ZDB Id:
2205412-1
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