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Molecular biology and spill-over potential of bat influenza A-like viruses

Subject Area Virology
Term from 2016 to 2023
Project identifier Deutsche Forschungsgemeinschaft (DFG) - Project number 285723639
 
Final Report Year 2024

Final Report Abstract

Previous understanding of the host range and diversity of influenza A virus (IAV) has been challenged by the discovery of two novel influenza A subtypes in Central and South American bat species. In 2012, a new influenza virus genome sequence was identified in frugivorous yellow-shouldered bats (Sturnira lilium) in Guatemala and tentatively named H17N10. Only one year later, a distinct influenza genome was isolated from the flat-faced fruit bat (Artibeus planirostris) in Peru and provisionally classified as H18N11. Serological surveys of Central and South American bat populations revealed a broad prevalence of H17/H18-specific antibodies, suggesting widespread circulation of these viruses among different bat species. Phylogenetic analysis of these bat-derived influenza virus genomes revealed that most genes were related to those of conventional IAV. Notable exceptions were the putative bat-derived HA and NA genes, which showed little homology with their counterparts from other IAV. Furthermore, biochemical data convincingly demonstrated that the surface glycoproteins of both H17N10 and H18N11 lack the canonical receptor-binding and receptor-destroying activities of conventional HA and NA, respectively. Recently, a new bat IAV was identified in Egypt. These bat influenza viruses of subtype H9N2 were included in our studies, especially since their zoonotic potential is unclear. This allowed us to study bat influenza viruses from both New World and Old World bats. In the first funding period, we successfully identified the underlying mechanisms causing reassortment incompatibility with conventional IAV, generated the first wild-type bat IAV by reverse genetics, identified the entry receptor required for cell entry, and analyzed the potential of H18N11 to grow in different species, including bats, in pilot studies. In the second funding period, by infecting A. Jamaicansas with H18N11, we were able to show that viral replication occurs primarily in the gut and that transmission between bats is very efficient. However, we also showed that H18N11 is poorly adapted to non-bat species such as mice, pigs or ferrets, suggesting a low zoonotic potential of these bat-borne viruses. We also showed that other bat species, such as Carollia perspicillata, are susceptible to H18N11, although no transmission between these bats was observed. Finally, by analyzing Bat H9N2, an emerging virus circulating in African bats, in vitro and in vivo, we found that these viruses share some unexpected pre-pandemic characteristics that warrant further investigation.

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