Rhinovirus infection alters cellular architecture of highly differentiated airway epithelial cells
Bibliographic record
Abstract
RATIONALE Human rhinoviruses (HRV) are responsible for over 50% of viral respiratory tract infections, and pose a significant health challenge for sufferers of chronic inflammatory airway diseases. Much of our current knowledge of the HRV lifecycle is based on other picornavirus models using cell lines of non‐airway origin (e.g. HeLa cells). However, the human airway epithelial cell (HAE) is the natural host cell that is subject to HRV infection and replication. Using highly‐differentiated HAE, we seek to elucidate the mechanisms that HRV uses to remodel the cellular architecture of HAE during replication, and to temporally relate these alterations to transient intercellular junctional changes. METHODS Highly differentiated air‐liquid interface (ALI) cultures of HAE, isolated from normal human lungs, were treated with three different HRV serotypes: HRV‐16, HRV‐1A, and HRV‐C15 for 24, 48, 72, 96, 120, 144 hours, and the junctional protein, ZO‐1, was examined. Studies of the architecture of the cytoskeleton were conducted using HAEs grown in monolayer submersion culture. Other stimuli include replication‐deficient HRV, poly(I:C) (a mimic of the double‐stranded RNA produced during HRV replication), cytochalasin D (actin disruptor), and paclitaxel (microtubule stabilizer). Cells were fixed for immunofluorescence using a resonance scanning confocal microscope. HRV replication kinetics were determined by serially washing ALI cultures every 24 hours to determine viral release by RT‐qPCR. Barrier function studies in Ussing chambers used FITC‐dextran (permeability) and measured real‐time transepithelial electrical resistance (TEER). RESULTS HRV‐1A and HRV‐C15, but not HRV‐16 induce dramatic remodeling of cellular architecture in highly differentiated HAE. These changes included the co‐localization of nuclei with apically expressed ZO‐1. This response depends upon the replication cycle of HRV, as replication‐deficient HRV does not induce these changes. Additionally, the cells associated with remodeled architecture are positive for HRV infection, as assessed by expression of replication intermediates. Preliminary data suggests that cytoskeletal inhibitors diminish the ability of HRV replication to occur, indicating a critical role for the actin cytoskeleton in HRV replication. CONCLUSION We conclude that some, but not all, HRV serotypes induce altered cellular architecture in HAE that is associated with disruption of the actin cytoskeleton. Future studies will seek to temporally relate altered cytoskeletal architecture with HRV replication sites. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".