Marine Lemesle, ANSES

Marine Lemesle (1), Pascal Dujardin (1), Grégory Caignard (1), Aurore fablet (1), Stéphan Zientara (1), Damien Vitour (1) (1): UMR 1161 VIROLOGIE, INRAe, ENVA, ANSES, Laboratory for Animal Health, Paris Est University, 94701 Maisons-Alfort, France.

Virus Replication: Entry, Exit and Everything in Between

African horse sickness virus (AHSV) is an orbivirus that leads to dramatic epizootics representing global threat to the equine livestock. The 9 serotypes are transmitted exclusively by Culicoides and the virus is currently endemic in tropical and subtropical areas of Africa. Recent European and Thai outbreaks, partly due to climate change, in previously unaffected regions suggest that AHSV is a ticking time bomb for the global equine industry. The virus induces a hemorrhagic disease leading to severe respiratory and circulatory disorders that are fatal for nearly 90% of horses (hyperacute forms kill animals within 48h). As AHSV is an obligate intracellular pathogen, its replication cycle requires the hijacking of host cell signaling pathways. This process, mainly due to virus-host protein-protein interactions, had poorly been studied for AHSV. To identify its virulence factors, we compared the interactome of a virulent AHSV-5 strain and a low-pathogenic AHSV-4 strain using a yeast two-hybrid (Y2H) system. Most of AHSV’s interactors identified interact with the viral proteins VP2, VP3, NS2, and NS3. Among the 64 interactors identified, it is interesting to note that 10 are restricted to the virulent serotype. GOterm analyses and functional studies showed that AHSV interactor list is significantly enriched for the following biological processes: host-virus interaction, innate immune response, and viral replication. The functional analysis of these interactions has paved the way for the development of strategies targeting virulence mechanisms to strengthen our ability to combat this devastating disease.