Propagation of respiratory viruses in human airway epithelia reveals persistent virus-specific signatures

Essaidi-Laziosi, Manel; Brito, Francisco; Benaoudia, Sacha; Royston, Léna; Cagno, Valeria; Fernandes-Rocha, Mélanie; Piuz, Isabelle; Zdobnov, Evgeny M.; Huang, Song; Constant, Samuel; Boldi, Marc-Olivier; Kaiser, Laurent; Tapparel, Caroline

doi:10.1016/j.jaci.2017.07.018

Cited by 104 publications

(168 citation statements)

References 56 publications

(63 reference statements)

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“…In fact, ALI epithelium was reported to demonstrate robust RSV replication (Villenave et al, ; Pickles, ), and the level of RSV load was similar to that observed in nasal washes from RSV infected infants (DeVincenzo et al, ) or after nasal challenge with RSV Memphis 37 strain to healthy subjects (Kelly et al, ). Thus, ALI epithelium is now being used as a model to study the behaviour of respiratory pathogens in human tissue (Essaidi‐Laziosi et al, ).…”

Section: Introductionmentioning

confidence: 99%

Late therapeutic intervention with a respiratory syncytial virus L‐protein polymerase inhibitor, PC786, on respiratory syncytial virus infection in human airway epithelium

Brookes¹,

Coates²,

Allen³

et al. 2018

British J Pharmacology

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Background and PurposeEffective anti‐respiratory syncytial virus (RSV) agents are still not available for clinical use. Current major targets are virus surface proteins, such as a fusion protein involved in viral entry, but agents effective after RSV infection is established are required. Here we have investigated the effects of late therapeutic intervention with a novel inhaled RSV polymerase inhibitor, PC786, on RSV infection in human airway epithelium.Experimental ApproachAir liquid interface‐cultured bronchial or small airway epithelium was infected with RSVA2. PC786 was applied apically or basolaterally once daily following peak virus load on Day 3 post inoculation. Apical wash was collected daily for determination of viral burden by PCR and plaque assay (primary endpoints) and biomarker analyses. The effects were compared with those of ALS‐8112, an anti‐RSV nucleoside analogue, and GS‐5806, a fusion‐protein inhibitor, which were treated basolaterally.Key ResultsLate intervention with GS‐5806 did not show significant anti‐viral effects, but PC786 produced potent, concentration‐dependent inhibition of viral replication with viral load falling below detectable limits 3 days after treatment commenced in airway epithelium. These effects were superior to those of ALS‐8112. PC786 showed inhibitory activities against RSV‐induced increases of CCL5, IL‐6, double‐strand DNA and mucin. The effects of PC786 were also confirmed in small airway epithelium.Conclusion and ImplicationsLate therapeutic intervention with the RSV polymerase inhibitor, PC786, reduced the viral burden quickly in human airway epithelium. Thus, PC786 demonstrates the potential to be an effective therapeutic agent to treat active RSV infection.

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Section: Introductionmentioning

confidence: 99%

Late therapeutic intervention with a respiratory syncytial virus L‐protein polymerase inhibitor, PC786, on respiratory syncytial virus infection in human airway epithelium

Brookes¹,

Coates²,

Allen³

et al. 2018

British J Pharmacology

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“…The activity of the main epithelial ionic channels, such as CFTR, EnaC, Na/K ATPase, is preserved and the epithelia is shown to respond in a regulated and vectorial manner to the pro-inflammatory stimulus, TNF-a (27) . A large panel of Most importantly, MucilAir™ replicates the main function of the airway epithelial cells, the mucociliary clearance driven by synchronized cilia-beating, and has been successfully used for acute, long-term and chronic in vitro studies (16,17,28,29) . Given that MucilAir™ is functionally robust and successfully mimics human nasal epithelium, it is important to conduct a clinical trial with SSPCF in order to demonstrate the safety and efficacy of it in in vivo settings.…”

Section: Discussionmentioning

confidence: 99%

“…The in vitro assays were performed in a 3D reconstituted human nasal epithelium model, MucilAir™ (Epithelix Sàrl, Geneva, Switzerland) for its great potential as a model to test respiratory sensitizers (16,17) . For maintenance, inserts were incubated in 500µl of MucilAir™ culture medium in a CO 2 incubator (37ºC, 5% CO 2 , 100% humidity, Heracell).…”

Section: Biological Model (Test System) Used For the In Vitro Studiesmentioning

confidence: 99%

Efficacy of a seawater solution enriched with copper, hyaluronic acid and eucalyptus against nasal pathogens

Huang¹,

Constant²,

Servi³

et al. 2019

RHINOL

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Background: Common cold is the most common disease which mainly affects the upper respiratory system. It is caused by viral or, in a small percentage, by bacterial infections. Current therapy options focus on symptomatic relief of the disease such as nasal saline irrigation, an easy-to-apply, comfortable, non-toxic method. In this study, a novel hypertonic seawater solution enriched with hyaluronic acids, eucalyptus oil, copper and manganese salts, Stérimar Stop & Protect Cold and Flu (SSPCF), has been investigated with respect to efficacy against viral and microbial infections. Methodology: An in vitro 3D reconstituted human nasal epithelium tissue model, MucilAir™, has been used in this study. Pretreatment and post-treatment anti-viral effects of SSPCF was measured through HRV-A16 viral load assays in order to evaluate the preventive and therapeutic efficacy of SSPCF, respectively. Anti-bacterial effects of SSPCF was assessed via Staphylococcus (S.) aureus growth inhibition and fluorescence bead-based phagocytosis assays. Results: One-hour SSPCF treatment pre-or post-viral infection inhibited the viral replication up to 99.78 and 59.91%, respectively. S. aureus growth was completely eliminated (100%) in SSPCF treated tissues after 1 hour of treatment. Phagocytosis rate was 3.28 folds higher in SSPCF treated tissue as compared to saline treated controls. Conclusions: Under the conditions of this in vitro study, SSPCF appears effective against some species of rhinoviruses (as in common cold) and S. aureus in vitro.

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“…Additionally, there are also evidence of reduced type I (IFNβ) and III (IFNλ) interferon production due to type 2-skewed inflammation, which contributes to imperfect clearance of the virus resulting in persistence of viral components, or the live virus in the airway epithelium (Contoli et al, 2006;Hwang et al, 2019;Wark, 2019). Due to the viral components remaining in the airway, antiviral genes such as type I interferons, inflammasome activating factors and cytokines remained activated resulting in prolong airway inflammation (Wood et al, 2011;Essaidi-Laziosi et al, 2018). These factors enhance granulocyte infiltration thus prolonging the exacerbation symptoms.…”

Section: Increase Viral Susceptibility and Prolong Activation Of Inflmentioning

confidence: 99%

Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium

Tan

Lim

Liu

et al. 2020

Front. Cell Dev. Biol.

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Respiratory virus infection is one of the major sources of exacerbation of chronic airway inflammatory diseases. These exacerbations are associated with high morbidity and even mortality worldwide. The current understanding on viral-induced exacerbations is that viral infection increases airway inflammation which aggravates disease symptoms. Recent advances in in vitro air-liquid interface 3D cultures, organoid cultures and the use of novel human and animal challenge models have evoked new understandings as to the mechanisms of viral exacerbations. In this review, we will focus on recent novel findings that elucidate how respiratory viral infections alter the epithelial barrier in the airways, the upper airway microbial environment, epigenetic modifications including miRNA modulation, and other changes in immune responses throughout the upper and lower airways. First, we reviewed the prevalence of different respiratory viral infections in causing exacerbations in chronic airway inflammatory diseases. Subsequently we also summarized how recent models have expanded our appreciation of the mechanisms of viral-induced exacerbations. Further we highlighted the importance of the virome within the airway microbiome environment and its impact on subsequent bacterial infection. This review consolidates the understanding of viral induced exacerbation in chronic airway inflammatory diseases and indicates pathways that may be targeted for more effective management of chronic inflammatory diseases.

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Propagation of respiratory viruses in human airway epithelia reveals persistent virus-specific signatures

Cited by 104 publications

References 56 publications

Late therapeutic intervention with a respiratory syncytial virus L‐protein polymerase inhibitor, PC786, on respiratory syncytial virus infection in human airway epithelium

Late therapeutic intervention with a respiratory syncytial virus L‐protein polymerase inhibitor, PC786, on respiratory syncytial virus infection in human airway epithelium

Efficacy of a seawater solution enriched with copper, hyaluronic acid and eucalyptus against nasal pathogens

Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium

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