Circulation of parahenipaviruses in shrews and assessment of their zoonotic potential in France – Henipa-ECO

For more than two decades, Nipah and Hendra viruses have been recognized as among the most deadly zoonotic viruses for humans. These viruses are transmitted by bats of the genus Pteropus in Asia and Australia. Recent research has expanded the number of known henipaviruses within the Paramyxoviridae family and described viruses of a new genus within this family, the parahenipaviruses, found in shrews from Africa, Asia, and Europe. This new genus includes two pathogenic viruses identified in China, called Langya and Mojiang. Partners in this project have already identified the circulation of several parahenipaviruses in French shrews, including known viruses (Denwin and Ninorex) and novel viruses. Initial characterization of the virus has shown that human cells, as well as many other mammalian cells, possess an entry receptor compatible with Denwin virus and that its P protein can disrupt interferon signaling. These shrew parahenipaviruses have several unique features that merit evaluation, including: 1/ an unknown pattern of virus spread within and between populations that may explain their exceptionally high prevalence; 2/ their potential zoonotic risks; and 3/ at a more molecular level, the role of their specific additional open reading frames, whose functions are currently unknown. In the Henipa-Eco project, we propose a multidimensional approach focused on complementary lines of investigation: 1/ study of the relationship between the diversity of parahenipaviruses and their natural hosts at the ecological scale; 2/ understanding the viral cycle and viral shedding at the individual level; and 3/ characterization, at the cellular level, of the response of human cells to parahenipaviruses and evaluation of the role of unknown viral proteins. To carry out this project, we will implement several key programs, including the collection, screening and inventory of more than 800 shrews and their genetic characterization, the establishment of a captive model of experimental infection and the generation of a reverse genetics system for Denwin virus. This “One Health” project aims to bring together the knowledge and expertise of virologists, mammalogists, immunologists, ecologists and wildlife specialists to provide a more detailed description of the diversity of parahenipaviruses and their circulation in reservoir hosts, through field studies and modeling to understand the impact of ecological factors. At the same time, we will seek to better understand their biology and provide key insights into their ability to cause disease in humans.