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Interaction of Influenza A virus with pathogenic and commensal bacteria

English title Interaction of Influenza A virus with pathogenic and commensal bacteria
Applicant Schmolke Mirco
Number 155949
Funding scheme Project funding (Div. I-III)
Research institution Dépt Microbiologie et Médecine Moléculaire Faculté de Médecine Université de Genève
Institution of higher education University of Geneva - GE
Main discipline Experimental Microbiology
Start/End 01.10.2014 - 30.09.2018
Approved amount 497'503.00
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All Disciplines (2)

Discipline
Experimental Microbiology
Immunology, Immunopathology

Keywords (4)

PB1-F2; Bacterial super infection; Influenza A virus; Microbiome

Lay Summary (German)

Lead
Viren benötigen zur Vermehrung die Hilfe von Wirtsorganismen. Sobald eine Wirtzelle infiziert ist, manipuliert das Virus eine Vielzahl von Prozessen in der Zelle, sowie im umliegenden Gewebe zu seinem Vorteil (z.B. um der Immunantwort zu entgehen oder um effizient seine eigenen Genprodukte zu produzieren). Influenza A Viren (Grippeviren) sind perfekt an die Vermehrung im Menschen angepasst und ein ideales Modelsystem, um den Einfluss von Virusinfektionen auf den Wirtsorganimus zu untersuchen.
Lay summary
Dank neuer Techniken ist unser Verständnis für die Effekte von Grippeviren auf infizierte Zellen in den letzen Jahren drastisch gewachsen.
Neuste Daten zeigen, dass Grippeviren nicht nur körpereigene Zellen beeinflussen, sondern auch symbiotische Bakterien. Symbiotische Bakterien (sog. “commensals”) besiedeln praktisch jede Körperoberfläche und sind in eine Vielzahl von physiologischen Prozessen eingebunden. Ihre Zusammensetzung beinflusst u.a. das Immunsystem und den Stoffwechsel. In den letzten Jahren haben zellkultur-unabhängige Techniken dazu beigetragen, die exakte Zusammensetzung des menschlichen Mikrobioms (Gesamtheit von Mikrorganismen in einer definierten Nische) zu identifizieren.
Dieses Forschungsprojekt wird beitragen, zu Verstehen, wie Grippeviren die Zusammensetzung von symbiotischen Bakterien beeinflussen und welche Konsequenzen dies für den Wirtsorganismus hat. Wir erhoffen uns aus diesem Forschungsvorhaben tiefere Einblicke in die komplexe Wechselwirkung von Virus und Wirt, die die Grundlage für neue diagnostische und therepeutische Ansätze in der Infektionsmedizin bilden könnten.
Direct link to Lay Summary Last update: 07.10.2014

Responsible applicant and co-applicants

Employees

Publications

Publication
Phosphoproteomic-based kinase profiling early in influenza virus infection identifies GRK2 as antiviral drug target
Yángüez Emilio, Hunziker Annika, Dobay Maria Pamela, Yildiz Soner, Schading Simon, Elshina Elizaveta, Karakus Umut, Gehrig Peter, Grossmann Jonas, Dijkman Ronald, Schmolke Mirco, Stertz Silke (2018), Phosphoproteomic-based kinase profiling early in influenza virus infection identifies GRK2 as antiviral drug target, in Nature Communications, 9(1), 3679-3679.
Influenza A virus infection impacts systemic microbiota dynamics and causes quantitative enteric dysbiosis
Yildiz Soner, Mazel-Sanchez Béryl, Kandasamy Matheswaran, Manicassamy Balaji, Schmolke Mirco (2018), Influenza A virus infection impacts systemic microbiota dynamics and causes quantitative enteric dysbiosis, in Microbiome, 6(1), 9-9.
Influenza VirusMethods and Protocols
Anchisi Stéphanie, Gonçalves Ana Rita, Mazel-Sanchez Béryl, Cordey Samuel, Schmolke Mirco (2018), Influenza VirusMethods and Protocols, Springer New York, New York, NY.
H5N1 Influenza A Virus PB1-F2 Relieves HAX-1-Mediated Restriction of Avian Virus Polymerase PA in Human Lung Cells
Mazel-Sanchez B., Boal-Carvalho I., Silva F., Dijkman R., Schmolke M. (2018), H5N1 Influenza A Virus PB1-F2 Relieves HAX-1-Mediated Restriction of Avian Virus Polymerase PA in Human Lung Cells, in Journal of Virology, 92(11), e00425-18-e00425-18.
Overcoming the Neonatal Limitations of Inducing Germinal Centers through Liposome-Based Adjuvants Including C-Type Lectin Agonists Trehalose Dibehenate or Curdlan
Vono Maria, Eberhardt Christiane Sigrid, Mohr Elodie, Auderset Floriane, Christensen Dennis, Schmolke Mirco, Coler Rhea, Meinke Andreas, Andersen Peter, Lambert Paul-Henri, Mastelic-Gavillet Beatris, Siegrist Claire-Anne (2018), Overcoming the Neonatal Limitations of Inducing Germinal Centers through Liposome-Based Adjuvants Including C-Type Lectin Agonists Trehalose Dibehenate or Curdlan, in Frontiers in Immunology, 9, 381.
RIG-I Signaling Is Critical for Efficient Polyfunctional T Cell Responses during Influenza Virus Infection
Kandasamy Matheswaran, Suryawanshi Amol, Tundup Smanla, Perez Jasmine T., Schmolke Mirco, Manicassamy Santhakumar, Manicassamy Balaji (2016), RIG-I Signaling Is Critical for Efficient Polyfunctional T Cell Responses during Influenza Virus Infection, in PLOS Pathogens, 12(7), e1005754-e1005754.

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
Swiss Virology Meeting 2018 Poster H5N1 INFLUENZA A VIRUS PB1-F2 SUPPRESSES PYROPTOTIC CELL DEATH AND SECRETION OF IL-1β 31.01.2018 Fribourg, Switzerland Boal Palheiros Torres de Carvalho Inês; Yildiz Soner; Schmolke Mirco;
Negative Strand Virus meeting Verona 2018 Individual talk H5N1 Influenza A Virus PB1-F2 Relieves HAX-1-Mediated Restriction of Avian Virus Polymerase PA in Human Lung Cells. 17.06.2017 Verona, Italy Schmolke Mirco; Boal Palheiros Torres de Carvalho Inês;
Swiss Virology Meeting 2016 Poster A Novel IVT RNA Based Vaccine Platform 02.02.2016 Thun, Switzerland Schmolke Mirco; Yildiz Soner;


Communication with the public

Communication Title Media Place Year
Media relations: print media, online media Comment on Mazel Sanchez et al ASM Microbe International 2018

Associated projects

Number Title Start Funding scheme
182475 Long-term consequences of microbiota alterations for host physiology after acute respiratory infections in childhood 01.10.2018 Project funding (Div. I-III)

Abstract

Influenza A virus (IAV) is a major human respiratory pathogen causing outbreaks with annual global attack rates of 5-10% for adults and 20-30% for children, resulting in estimated 5 million severe cases annually, 250000-500000 with fatal outcome (estimated numbers by World Health Organization (WHO, http://www.who.int/mediacentre/factsheets/fs211/en/ and http://www.who.int/biologicals/ vaccines/influenza/en/ ). High-risk groups include infants, elderly and immune compromised patients. One of the major complications in IAV infections is bacterial super infection. During the 1918 Spanish influenza outbreak the majority of infected patients died of bacterial super infections. Even less devastating seasonal influenza infections result in bacterial super infections in up to 15% of the cases. The mechanisms by which IAV supports this subsequent super infection with pathogenic respiratory bacteria like Streptococcus pneumoniae, Staphylococcus aureus or Haemophilus influenzae are matter of ongoing research. Viral pathogenicity factors like the accessory protein PB1-F2 have been shown to enhance bacterial super infections in animal models, although the mechanisms of this enhancement are far from being understood. Recent reports indicate that IAV infections not only increase susceptibility of super infections with pathogenic bacteria but significantly impact the composition of host lung microbiota. At the same time host microbiota are required for efficient priming of immune responses against IAV infections. To better understand the triangular relationship of host, microbiota and invading virus we propose experiments that will address the impact of host innate immunity on microbiome composition during IAV infection. We will test if and how pathogenicity factors like PB1-F2 affect the composition of the host microbiome during IAV infection. Furthermore, we will determine if these changes in microbiome influence the host susceptibility towards bacterial super infections, which in the long run might help to discriminate between useful, expendable or harmful commensal bacteria. Finally, we are aiming to understand how IAV PB1-F2 increases susceptibility to bacterial super infection on a molecular level, by identification of host factors that interact with PB1-F2. The suggested projects could reveal new diagnostic markers that can be used to determine when use of antibiotics is likely to prevent super infections after IAV infection and identify host factors that might contribute to bacterial super infection.
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