Transcriptomics of rhinovirus persistence reveals sustained expression of RIG-I and interferon-stimulated genes in nasal epithelial cells in vitro.
Allergy
; 77(9): 2778-2793, 2022 09.
Article
en En
| MEDLINE
| ID: mdl-35274302
ABSTRACT
BACKGROUND:
Human rhinoviruses (HRVs) are frequently associated with asthma exacerbations, and have been found in the airways of asthmatic patients. While HRV-induced acute infection is well-documented, it is less clear whether the nasal epithelium sustains prolonged HRV infections along with the associated activation of host immune responses.OBJECTIVE:
To investigate sustainably regulated host responses of human nasal epithelial cells (hNECs) during HRV persistence.METHODS:
Using a time-course study, HRV16 persistence and viral replication dynamics were established using an in vitro infection model of hNECs. RNA sequencing was performed on hNECs in the early and late stages of infection at 3 and 14 days post-infection (dpi), respectively. The functional enrichment of differentially expressed genes (DEGs) was evaluated using gene ontology (GO) and Ingenuity pathway analysis.RESULTS:
HRV RNA and protein expression persisted throughout prolonged infections, even after decreased production of infectious virus progeny. GO analysis of unique DEGs indicated altered regulation of pathways related to ciliary function and airway remodeling at 3 dpi and serine-type endopeptidase activity at 14 dpi. The functional enrichment of shared DEGs between the two time-points was related to interferon (IFN) and cytoplasmic pattern recognition receptor (PRR) signaling pathways. Validation of the sustained regulation of candidate genes confirmed the persistent expression of RIG-I and revealed its close co-regulation with interferon-stimulated genes (ISGs) during HRV persistence.CONCLUSIONS:
The persistence of HRV RNA does not necessarily indicate an active infection during prolonged infection. The sustained expression of RIG-I and ISGs in response to viral RNA persistence highlights the importance of assessing how immune-activating host factors can change during active HRV infection and the immune regulation that persists thereafter.Palabras clave
Texto completo:
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Banco de datos:
MEDLINE
Asunto principal:
Asma
/
Rhinovirus
/
Receptores de Ácido Retinoico
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Allergy
Año:
2022
Tipo del documento:
Article
País de afiliación:
Singapur