Research Project:
Molecular characterization of Influenza D virus - host interactions

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cris.legacyIdpj00093en_US
cris.sourceIdINTERNAL-SUBMISSION::6de8379c-3484-4729-a7a9-ecbd808f3a67en_US
cris.sourceIdMIGRATION::pj00093
crispj.coinvestigator.affiliationInstitute for Infectious Diseasesen_US
crispj.coinvestigator.affiliationInstitute for Infectious Diseases, Researchen_US
crispj.coinvestigator.affiliationInstitute for Infectious Diseases, Researchen_US
crispj.coinvestigatorsDijkman, Ronalden_US
crispj.coinvestigatorsLaloli, Lauraen_US
crispj.coinvestigatorsProbst, Lukas Martinen_US
crispj.coordinatorInstitute for Infectious Diseases, Researchen_US
crispj.investigatorDijkman, Ronalden_US
crispj.investigator.affiliationInstitute for Infectious Diseasesen_US
crispj.partnerouInstitute for Infectious Diseases, Researchen_US
datacite.rightsmetadata.only
dc.date.accessioned2023-01-03T10:36:46Z
dc.date.available2024-07-01T10:37:20Z
dc.description.abstractBackground: Influenza viruses are notorious pathogens that frequently cross the species barrier with often severe consequences for both animal and human health. In 2011, a novel member of the Orthomyxoviridae family, Influenza D virus (IDV), was identified in the respiratory tract of pigs with influenza-like symptoms and subsequently also in cattle, a species that previously never was considered to be susceptible to influenza virus infection. Epidemiological surveys among livestock demonstrated that Influenza D virus is worldwide distributed among cattle, swine, goat and sheep, but the most striking is the detection of influenza D virus directed antibodies among humans with occupational exposure to livestock. Influenza D virus is phylogenetic closely related to the human influenza C virus that utilize the same cellular receptor determinant, however, influenza C virus infections are predominantly restricted to humans, whereas the novel influenza D virus has a promiscuous host tropism. The underlying molecular viral and host determinants affecting the broad host tropism of influenza D virus remain elusive, and considering the zoonotic potential, interspecies transmission and the important veterinary and public health significance of influenza viruses, the molecular characterization of influenza D virus – host interactions is warranted. Working hypothesis and aims: In cattle and swine the respiratory epithelium has shown to be the main entry port of IDV and is an important barrier to infection. Herein the innate immune system has a major protective role as the first line of defence in the barrier function. My hypothesis is that the receptor determinant (9-O-Ac-Neu5Ac) of IDV is distributed in a cell-type specific fashion and that this influences the dynamics of the host innate immune response, and that this may differ among host species. In addition, I hypothesize that the non-structural 1 (NS1) protein of IDV is a potent virulence factor that plays an important role in antagonising the innate immune response and, like other influenza viruses, influences the host range. As a first step toward identifying viral traits involved in the broad host tropism of the newly emerging influenza D virus we will determine the (i) cell and host tropism and (ii) innate immune response at the primary site of replication using in vitro respiratory epithelium models of cattle, swine, and human. Furthermore, we will (iii) molecular characterize the NS1 protein on its role in innate immune response antagonism in those different species. In combination, with the other aims we will perform a (iv) novel complementary genome-wide CRISPR-based screen to identify host determinants impeding influenza D virus replication. Expected significance: The proposed studies will provide detailed knowledge on the host tropism of influenza D virus and innate immune response during viral infections among different species and will reveal whether IDV possess zoonotic potential. Moreover, it provides a comprehensive overview on the innate immune system among livestock and the role of IDV NS1 protein as an important antagonist of this system. This knowledge is indispensable to understand the basic parameters of the successful establishment of IVD among different livestock species and will be highly instructive when assessing the risk of other influenza virus family members in animals and humans.en_US
dc.description.sponsorshipInstitute for Infectious Diseases
dc.description.sponsorshipInstitute for Infectious Diseases, Research
dc.identifier.urihttps://boris-portal.unibe.ch/handle/20.500.12422/31153
dc.language.isoenen_US
dc.relation.funding179260
dc.subjectDewey Decimal Classification::500 - Science::570 - Life sciences; biologyen_US
dc.subject.keywordsInfluenza virusen_US
dc.subject.keywordsInnate immunityen_US
dc.subject.keywordsHost - pathogen interactionen_US
dc.titleMolecular characterization of Influenza D virus - host interactionsen_US
dspace.entity.typeProject
oairecerif.project.endDate2022-12-31en_US
oairecerif.project.startDate2018-08-01en_US
unibe.isfundedtrueen_US
unibe.primaryconductorInstitute for Infectious Diseases, Researchen_US
unibe.project.duration01-08-2018 - 31-12-2022en_US
unibe.project.managerDijkman, Ronalden_US
unibe.project.primarycontactDijkman, Ronalden_US
unibe.projectManager.affiliationInstitute for Infectious Diseasesen_US
unibe.projectprimarycontact.affiliationInstitute for Infectious Diseasesen_US
unibe.publication.borisid132999en_US
unibe.publication.borisid154365en_US
unibe.publication.borisid172732en_US
unibe.publication.borisid151144en_US
unibe.publication.borisid174001en_US
unibe.publication.titleHolwerda, Melle; Kelly, Jenna; Laloli, Laura; Stürmer, Isabel; Portmann, Jasmine; Stalder, Hanspeter; Dijkman, Ronald (2019). Determining the Replication Kinetics and Cellular Tropism of Influenza D Virus on Primary Well-Differentiated Human Airway Epithelial Cells. Viruses, 11(4) Molecular Diversity Preservation International MDPI 10.3390/v11040377 <http://dx.doi.org/10.3390/v11040377>en_US
unibe.publication.titleHolwerda, Melle; Laloli, Laura; Wider, Manon; Schönecker, Lutz; Becker, Jens; Meylan, Mireille; Dijkman, Ronald (2021). Establishment of a Reverse Genetic System from a Bovine Derived Influenza D Virus Isolate. Viruses, 13(3) Molecular Diversity Preservation International MDPI 10.3390/v13030502 <http://dx.doi.org/10.3390/v13030502>en_US
unibe.publication.titleLaloli, Laura; Licheri, Manon Flore; Probst, Lukas; Licheri, Matthias; Gultom, Mitra; Holwerda, Melle; V'kovski, Philip; Dijkman, Ronald (2022). Time-resolved characterization of the innate immune response in the respiratory epithelium of human, porcine, and bovine during influenza virus infection. Frontiers in immunology, 13, p. 970325. Frontiers Research Foundation 10.3389/fimmu.2022.970325 <http://dx.doi.org/10.3389/fimmu.2022.970325>en_US
unibe.publication.titleGultom, Mitra; Laloli, Laura; Dijkman, Ronald (2020). Well-Differentiated Primary Mammalian Airway Epithelial Cell Cultures. In: Maier, Helena J.; Bickerton, Erica (eds.) Coronaviruses. Methods and Protocols. Methods in Molecular Biology: Vol. 2203 (pp. 119-134). Humana, New York, NY 10.1007/978-1-0716-0900-2_10 <http://dx.doi.org/10.1007/978-1-0716-0900-2_10>en_US
unibe.publication.titleKelly, Jenna N; Laloli, Laura; V'kovski, Philip; Holwerda, Melle; Portmann, Jasmine; Thiel, Volker; Dijkman, Ronald (2022). Comprehensive single cell analysis of pandemic influenza A virus infection in the human airways uncovers cell-type specific host transcriptional signatures relevant for disease progression and pathogenesis. Frontiers in immunology, 13(978824), p. 978824. Frontiers Research Foundation 10.3389/fimmu.2022.978824 <http://dx.doi.org/10.3389/fimmu.2022.978824>en_US

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