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Entry and reassortment potential of the newly discovered bat influenza A-like viruses (Bat Influenza II)

Project

Food and consumer protection

This project contributes to the research aim 'Food and consumer protection'. Which funding institutions are active for this aim? What are the sub-aims? Take a look:
Food and consumer protection


Project code: FLI-IVD-08-Ri-0454
Contract period: 01.05.2016 - 31.07.2019
Purpose of research: Experimental development
Keywords: Veterinary medicine, diagnostic methods

In 2012 and 2013, two complete genome sequences of influenza A-like viruses, provisionally designated H17N10 and H18N11, were identified by next-generation sequencing in bat specimens. Despite considerable progress there are many questions that remain to be addressed: To date, no infectious viruses have been isolated or produced by reverse genetics, although we have succeeded in generating chimeric viruses containing six internal genes from these bat viruses and the surface glycoproteins HA and NA from conventional influenza A viruses (IAV). We could show that these chimeric viruses and conventional IAV cannot reassort and obtained preliminary data that this is due, amongst other reasons, to an ill-defined incompatibility of the viral nucleoprotein. Finally, unlike all conventional IAVs, the hemagglutinin (HA) and neuraminidase (NA) protein of these bat viruses do not bind to sialic acids, leaving the identity of the cellular receptor(s) and the complete entry mechanism obscure. In a collaborative effort, we want to address the major open questions, the identity of the entry receptor and the barriers to reassortment with conventional IAV, and generate full infectious bat IAV. Specifically, we aim to a) identify the cellular receptor(s) of bat influenza A-like viruses and determine whether it is specifically expressed in bats, b) study the role of both HA and NA during viral infection, c) challenge our hypothesis that NP co-evolved differently between prototypic IAV and bat influenza A-like viruses resulting in virus subtype-specific packaging of the viral segments, and d) generate authentic H17N10 or H18N11 viruses in vitro for further studies in vivo. This study has the potential to uncover the entry mechanism of bat influenza A-like viruses, the role of NP in genome packaging, the function of the atypical HAs and NAs, and finally the spill-over potential of these viruses to other animals. This highly collaborative project depends on essential contributions of all three partners due to the different expertise represented by each partner and the intertwined nature of the projects.

- Receptor identified (1) - Bat flu virus could be propagated (2) - Whole genome sequencing (2) - Infection trials with ferrets (2) - Infection trials with Seba's Short-Tailed Bats (2) (1) Karakus et al. MHC class II proteins mediate cross-species entry of bat influenza viruses. Nature. 2019 Mar;567(7746):109-112. doi: 10.1038/s41586-019-0955-3. (2) Ciminski et al. Bat influenza viruses transmit among bats but are poorly adapted to non-bat species. Nat Microbiol. 2019 Dec;4(12):2298-2309. doi: 10.1038/s41564-019-0556-9. (3) Gorka et al. Characterization of Experimental Oro-Nasal Inoculation of Seba's Short-Tailed Bats (Carollia perspicillata) with Bat Influenza A Virus H18N11. Viruses. 2020 Feb 19;12(2). pii: E232. doi: 10.3390/v12020232.

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Subjects

Framework programme

BMEL Frameworkprogramme 2008

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