The MHC class-II HLA-DR receptor mediates bat influenza A-like H17N10 virus entry into mammalian cells
Please arrive 5 minutes before the seminar starts to gain access to the building.
Bats are notorious reservoirs of diverse, potentially zoonotic viruses, exemplified by the evolutionarily distinct, influenza A-like viruses H17N10 and H18N11 (BatIVs). The surface glycoproteins [haemagglutinin (H) and neuraminidase (N)] of BatIVs neither bind nor cleave sialic acid receptors, which suggests that these viruses employ cell attachment and entry mechanisms that differ from those of classical influenza A viruses (IAVs). Identifying the cellular factors that mediate entry and determine susceptibility to infection will help assess the host range of BatIVs. Here, we investigated a range of cell lines from different species for their susceptibility to infection by pseudotyped viruses (PV) 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 (H17-PV). We observed with microarrays and qRT-PCR 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 elucidate its zoonotic transmission.
Date: 15 May 2019, 12:00
Venue: Medawar Building, off South Parks Road OX1 3SY
Venue Details: Seminar room, South Parks Road, Oxford, OX1 3SY
Speaker: Efstathios Giotis (Imperial College London)
Organising department: Nuffield Department of Clinical Medicine
Organisers: Dr Proochista Ariana (University of Oxford), Professor Sunetra Gupta (University of Oxford), Prof Lynn Dustin (NDORMS)
Organiser contact email address: suki.kenth@ndm.ox.ac.uk
Host: Emilia Skirmuntt (Department of Zoology)
Part of: Peter Medawar Building Seminars
Booking required?: Not required
Cost: FREE
Audience: Members of the University only
Editor: Suki Kenth