The rapid advances in sequencing and computational technologies accompanied by a drastic reduction of sequencing costs have revolutionized microbial genomics and provided an unprecedented insight into microbial evolution, diversity, and host–pathogen interaction. Moreover, genomic technologies demonstrated great potential and suitability for clinical diagnostics or the real-time detection and surveillance of epidemics. The overall goal of the PREPMedVet partners (FLI, BNITM, ANSES, and AMU) is to set up a portable diagnostic sequencing platform capable to deliver in a clinically relevant turnaround time critical information in the context of an outbreak. The consortium has aimed to develop a standard wet-lab protocol which could be applied on-site using portable next-generation sequencing platforms and user-friendly sequence analysis software’s capable to deliver valuable insight into epidemic transmission patterns, pathogen genomics, evolution and the possible source of origin. The identification of pathogens will be flanked by production and validation of easy-to-use detection assays that can be stockpiled, transported, and delivered to the end users for timely and comprehensive reaction on outbreak scenarios. The project PREPMedVet combines French and German key partners relevant in Human and Animal Health in a One Health approach and integrates relevant multiplying end users from the field.

The project aims at studying the emergence and re-emergence of pathogenic lagoviruses, notably by exploring the hypothesis of a species jump involving introduction of a reservoir host species. RHDV and EBHSV are RNA viruses of the genus Lagovirus (Caliciviridae) affecting European rabbit (OC) and Brown hare (LE), respectively. They are responsible for two distinct diseases RHD (Rabbit Hemorrhagic Disease) and EBHS (European Brown Hare Syndrome) that emerged in the early 1980s. RHD in particular causes high mortalities in wildlife and domestic rabbits, threatening the European rabbit industry. Its impact was controlled by vaccination until the emergence in 2010 in France of a genetically distant variant (RHDV2). This new lagovirus partially escapes immunity and has quickly spread throughout France and subsequently has reached adjacent countries, resulting in re-emergence of the disease both in domestic and wild populations. RHDV2 is able to infect the SardinianCape hare causing an RHDV-like disease. This is the first account of interspecies transmission of a lagovirus between European leporids. Two competing hypotheses can be put forward to attempt to explain RHDV and EBHSV origin and the emergence of RHDV2: the evolution from pre-existing non-pathogenic (NP) viruses circulating in European leporids, or a species jump from Sylvilagus floridanus (SF). Indeed, several elements suggest that SF may be a reservoir of these viruses. This leporid species is exotic for Europe where it has been massively introduced from the end of 1970s to the late 1980s, which fits with the dates of emergence of the diseases. Preliminary data demonstrate the feasibility of a species jump since SF has been successfully infected by EBHSV. With a particular attention on RHDV, we will explore the possibility that RHDV and EBHSV, and later RHDV2, emerged following 1) viral evolution among known and unknown NP viruses infecting OC and LE, 2) species jumps of SF viruses which are pathogenic for recipient leporid species and/or have recombined with OC and LE NP viruses to give rise to highly pathogenic strains. Search for the genetic determinisms of pathogenicity would also contribute to understand how these lagoviruses acquired virulence, notably by studying the host-pathogen co-evolution through HBGA ligands polymorphism, by identifying the capsid protein codons under positive selection and establishing the role in infectivity and/or virulence of the potential glycosylation sites.