Project

Back to overview

Pathogenesis of Human rhinoviruses in the context of multiple infection

Applicant Essaidi-Laziosi Manel
Number 178708
Funding scheme Marie Heim-Voegtlin grants
Research institution Dépt Microbiologie et Médecine Moléculaire Faculté de Médecine Université de Genève
Institution of higher education University of Geneva - GE
Main discipline Medical Microbiology
Start/End 01.03.2018 - 31.08.2018
Approved amount 60'786.00
Show all

All Disciplines (2)

Discipline
Medical Microbiology
Immunology, Immunopathology

Keywords (5)

dual infection; host receptors; innate immunity; pathogenesis; respiratory viruses

Lay Summary (French)

Lead
Pathogenèse des virus respiratoires dans le contexte d'infection multiple
Lay summary

Les infections respiratoires virales constituent une cause de morbidité importante pour certaines populations vulnérables. Plusieurs virus respiratoires co-circulent pendant l’année et peuvent être co-detectés chez un même patient. De nombreuses études épidémiologiques ont suggéré des associations positives ou négatives entre ces différents virus. Cependant, le mécanisme expliquant ces associations reste peu clair. Je suis intéressée par l’étude de la pathogenèse virus respiratoires en utilisant un épithélium respiratoire différencié (Tapparel et al., virology, 2013) et des souches virales cliniques, mimant ainsi l’infection virale des voies respiratoires supérieures. Dans un premier projet, j’ai pu démontrer la pathogenèse différentielle de neuf des virus respiratoires les plus prévalents en clinique incluant des rhinovirus, le virus de la grippe, le coronavirus et le virus respiratoire syncytial (Essaidi-Laziosi et al., JACI, 2017). Dans mon projet en cours, j’envisage approfondir mon investigation en étudiant les interactions virus-virus dans le contexte d’infections multiples. Je suis intéressée par l’étude de la réponse immune innée potentiellement responsable du blocage ou de l’exacerbation de l’infection. Cette étude permettra, à court terme, d’élargir les connaissances sur la pathogénèse des différents virus respiratoires dans le contexte d’infections multiples ; et, à moyen et long termes, d’améliorer la gestion des patients à l’hôpital et d’éviter l’usage inapproprié de médicaments et/ou anti-viraux.

Direct link to Lay Summary Last update: 30.11.2017

Responsible applicant and co-applicants

Employees

Publications

Publication
Interferon-Dependent and Respiratory Virus-Specific Interference in Dual Infections of Airway Epithelia
Essaidi-Laziosi Manel, Geiser Johan, Huang Song, Constant Samuel, Kaiser Laurent, Tapparel Caroline (2020), Interferon-Dependent and Respiratory Virus-Specific Interference in Dual Infections of Airway Epithelia, in Scientific Reports, 10(1), 10246-10246.
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, Huang Song, Constant Samuel, Boldi Marc-Olivier, Kaiser Laurent, Tapparel Caroline (2018), Propagation of respiratory viruses in human airway epithelia reveals persistent virus-specific signatures, in Journal of Allergy and Clinical Immunology, 141(6), 2074-2084.
Viral chimeras decrypt the role of enterovirus capsid proteins in viral tropism, acid sensitivity and optimal growth temperature
Royston Léna, Essaidi-Laziosi Manel, Pérez-Rodríguez Francisco J., Piuz Isabelle, Geiser Johan, Krause Karl-Heinz, Huang Song, Constant Samuel, Kaiser Laurent, Garcin Dominique, Tapparel Caroline (2018), Viral chimeras decrypt the role of enterovirus capsid proteins in viral tropism, acid sensitivity and optimal growth temperature, in PLOS Pathogens, 14(4), e1006962-e1006962.

Collaboration

Group / person Country
Types of collaboration
INSTITUTE OF INFECTION, IMMUNITY & INFLAMMATION, University of Glasgow Great Britain and Northern Ireland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
CHU Quebec, Guy Boivin's Lab Canada (North America)
- Publication
Institute of Virology and Immunology university of Bern Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
elive 2018 Poster Replication of rhinovirus A, B and C and enterovirus D-68 in respiratory tissues originating from asthmatic patients and implication of CDHR3 06.07.2020 Nice, France Essaidi-Laziosi Manel;
Europic 2018 Poster Replication of rhinovirus A, B and C and enterovirus D-68 in respiratory tissues originating from asthmatic patients and implication of CDHR3 03.06.2018 Egmond aan Zee, Netherlands Essaidi-Laziosi Manel;


Awards

Title Year
prix 3R 2018

Associated projects

Number Title Start Funding scheme
158269 Réplication et pathogenése des rhinovirus humains dans le contexte de co-infections avec d’autres virus respiratoires 01.11.2015 Marie Heim-Voegtlin grants

Abstract

The human airway epithelium is the first line of defense against respiratory infections. Mucociliary clearance serves as a mechanical barrier against microorganisms while epithelial cells recognize and fight the infection via cytokine secretion. Viral respiratory infections are the most frequent causes of acute illnesses worldwide and cause mild to severe diseases such as common cold, bronchiolitis and pneumonia. Our project aims to study single and multiple viral infections by the most frequent human respiratory viruses using in vitro reconstituted human airway epithelia, a relevant model system mimicking the human respiratory epithelium. In the first achieved part, we infected in parallel, differentiated tissues with clinically relevant strains of rhinovirus, respiratory enterovirus, influenza virus, respiratory syncytial virus and coronavirus and different parameters were compared. For each virus, the replication kinetics, the cell tropism and the impact of the virus on tissue integrity and cytokine secretion was assessed. We showed that RVs, RSV-B and HCoV-OC43 infected only ciliated cells and caused no major cell death while H3N2 and EV-D68 caused massive ciliated cells loss, transient perturbation of tissue integrity and were detected in ciliated and non-ciliated cells. H3N2 was detected also in rare goblet and basal cells. All viruses except RV-B48 and HCoV-OC43 affected cilia beating and mucociliary clearance. Persistent replication was observed in all cases and was linked to moderate immune response rather than viral adaptation. This work provides insights on the different patterns of infection by the most prevalent respiratory viruses and on the interplay between the virus and the tissue response in the course of persistent infections. It was recently accepted for publication by Journal of Allergy and Clinical Immunology. In the second part of this project, we aim to study the consequences of multiple infections by distinct respiratory viruses in airway epithelia in terms of individual viral replication and tissue response. Preliminary data showed that Rhinovirus replication is inhibited by the presence of RSV-A and H1N1 but not HCoV-OC43 while H1N1 replication seems enhanced by a secondary RV infection. Deeper investigation is still needed in order to unveil the mechanism leading to virus-virus interactions. This study will provide important additional mechanistic clues regarding anti-viral innate immunity and virus pathogenesis and will help to handle optimally patients hospitalized with respiratory infections.
-