Chair and invited talk on bat influenza H17N10 at Emerging Viruses 2019 (Oxford, 9th Sept 2019)

On 9th Sept 2019 I am co-chairing a symposium on Emerging Viruses with Dr Wright (Sussex) and Dr Scott (Kent). During this symposium I will also deliver an invited talk entitled Tropism and neutralisation studies on bat influenza H17. This will cover research recently published in Nature Microbiology and in bioRxiv. This promises to be a very exciting meeting enabling the fostering of new collaborations between academia, public/animal health bodies and industry.

The abstract for my talk can be found below;

Tropism and neutralisation studies on bat influenza H17

Efstathios Giotis¹, George Carnell², Erik Young³, Saleena Ghanny³, Patricia Soteropoulos³, Antonello Pessi⁴, Krzysztof Lacek⁵, Simon Scott², Linfa Wang⁶, Wendy Barclay¹, Michael Skinner¹, Nigel Temperton²

 

¹Section of Virology, Department of Medicine, St Mary’s Campus, Imperial College London, UK.

²Viral Pseudotype Unit, Medway School of Pharmacy, University of Kent, Chatham, UK.

³Hackensack University Medical Center Department of Surgery, Hackensack, NJ, USA.

⁴Ceinge Biotecnologie Avanzate S.C.R.L., Napoli, Italy

⁵The Laboratory of Virus Molecular Biology, University of Gdansk, Gdansk, Poland

⁶Programme in Emerging Infectious Disease, Duke-NUS Medical School, Singapore

The diversity of subtypes within the Influenza A virus genus has recently expanded with the identification of H17N10 and H18N11 from bats. In order to further study the tropism and zoonotic potential of these viruses, we have successfully produced lentiviral pseudotypes bearing both haemagglutinin H17 and neuraminidase N10. We investigated a range of cell lines from different species for their susceptibility to infection by pseudotypes bearing bat H17 and/or N10 envelope glycoproteins. We show that a number of human haematopoietic cancer cell lines and the canine kidney MDCK II (but not MDCK I) cells are susceptible to H17 pseudotypes. Using microarrays and qRT-PCR we show that the dog leukocyte antigen DLA-DRA mRNA is over expressed in late passaged parental MDCK and commercial MDCK II cells, compared to early passaged parental MDCK and MDCK I cells, respectively. The human orthologue HLA-DRA encodes the alpha subunit of the MHC class II HLA-DR antigen-binding heterodimer. Small interfering RNA- or neutralizing antibody-targeting HLA-DRA, drastically reduced the susceptibility of Raji B cells to H17-PV. Conversely, over expression of HLA-DRA and its paralogue HLA-DRB1 on the surface of the unsusceptible HEK293T/17 cells conferred susceptibility to H17-PV. The identification of HLA-DR as an H17N10 entry mediator will contribute to a better understanding of the tropism of the virus and will help to elucidate its zoonotic transmission. Should this new influenza virus spill over into the human population we also show that H17 pseudotypes can be efficiently neutralised by the broadly-neutralizing HA2 stalk monoclonal antibodies CR9114 and FI6. Thus the lentiviral pseudotype system is a useful research tool, and amenable for investigation of bat influenza tropism, restriction and pandemic preparedness, without the constraints or safety issues with producing a replication-competent virus, to which the human population is naïve.