Head of Unit: Stéphan Zientara
Deputy Directors: Jennifer Richardson (INRAE), Nicole Pavio (ANSES) and Bernard Klonjkowski (ENVA).
The Virology Joint Research Unit (UMR), created in January 2002, is governed by three supervisory bodies: ANSES, the National Research Institute for Agriculture, Food and the Environment (INRAE) and the Alfort National Veterinary School (ENVA).
The research carried out within the UMR mainly covers three major strategic orientations: biology of viral infections, and interspecies transmission in particular; detection and epidemiology of emerging and re-emerging viral infections, and development of vaccines and antiviral therapies. The Virology UMR takes a comprehensive approach to veterinary public health research, with objectives ranging from the applied to the fundamental.
The Virology UMR has several national reference laboratory (NRL) mandates: Foot-and-mouth disease virus (FMDV), African horse sickness virus (AHSV), Bluetongue virus (BTV), Vesicular stomatitis, and West Nile virus.
It also holds two European Union Reference Laboratory (EURL) mandates: Foot-and-mouth disease, and Equine diseases (West Nile virus, Eastern, Western, Venezuelan and Japanese equine encephalitis viruses, and vesicular stomatitis virus).
At the international level, the unit is the World Organisation for Animal Health (WOAH) reference laboratory for foot-and-mouth disease virus and epizootic haemorrhagic disease. Lastly, it is an FAO Collaborating Centre for foot-and-mouth disease.
The unit, as an NRL, helps coordinate networks of about 60 regional laboratories in France. At the international level, it is involved in cross-border disease surveillance.
Expert appraisal activities
The Virology UMR conducts expert appraisals for international organisations such as WOAH, the FAO, the European Commission for the Control of Foot-and-mouth Disease (EuFMD), and the European Food Safety Authority (EFSA). Scientists from the unit are members of the Scientific Advisory Board of the Friedrich-Loeffler-Institut.
The unit studies zoonotic (transmissible to humans) or epizootic (animal epidemic) viruses of major importance for human and animal health. Its research activities include fundamental questions on the biology of viral agents, as well as applied research on epidemiology, vaccinology and the mechanisms of virus-host cell interactions. As an example, the UMR is assessing novel diagnostic tools for epidemiological surveillance and phylogenetic studies of animal viruses. There is a particular focus on the orbivirus and picornavirus groups of viruses, as well as on enteric viruses, the neurovirology of zoonoses (infection of the nervous system by viruses), the crossing of species barriers, adenovirus-derived vectors and vaccines.
The themes studied by the Virology UMR include:
- developing new diagnostic and prevention methods for major animal viral diseases (foot-and-mouth disease, bluetongue, equine viral diseases, etc.);
- coordinating epidemiology networks (West Nile virus, other equine viruses, bluetongue virus, etc.);
- analysing the risk of transmission from animals to humans (West Nile virus, Borna virus, coronavirus, picornavirus, hepatitis E virus, etc.);
- analysing the potential public health risks of animal viruses: virus-host interactions, interspecies transmission;
- generic approaches in vaccinology: development of new vectors associated with genes coding for major antigens of different economically important viruses;
- developing molecular tools for monitoring tick infection by zoonotic arboviruses.
Multi-scale eco-evolution of coronaviruses: from surveillance to emergence prediction
Funding: ERA-NET ICRAD
The objective of the MuseCoV project is to better understand the global circulation of animal coronaviruses (CoVs) and their genetic evolutionary dynamics in different ecological contexts. Samples collected over time from bats, domestic carnivores, ruminants, poultry and wild animals in different locations in Europe will be used to analyse their rates of genetic evolution under natural conditions. These studies will be supplemented by in vitro assays, which will assess the frequency of recombination between different viral strains in the same animal species (avian or porcine) when these strains are inoculated simultaneously onto cell cultures. The project's second objective will be to assess the circulation of SARS-CoV-2 in pets and domestic animals and to perform in vitro studies that will analyse its replication potential in cells from different animals.
Decoding a virus Achilles heel: the African swine fever virus interactome
Partners: project coordinated by ANSES. Involves INRAE, Friedrich-Loeffler-Institut (Germany), Pirbright Institute (UK), National Institute for Agricultural and Food Research and Technology (INIA, Spain) and the University of Tartu (Estonia).
Funding: ERA-NET ICRAD
African swine fever (ASF) is a contagious viral disease classified as a category 1 health hazard in France. It affects all domestic and wild swine and is characterised by high mortality in domestic pigs and European wild boar.
The ASFVint project consists in carrying out a large functional interactomics programme for the ASF virus: the objective is to identify interactions between viral and cell proteins for a wild and virulent strain of the ASF virus. This will enable new virulence and pathogenicity factors to be identified, which would be important molecular bases providing insights on the attenuation process.
From proteogenomic host response signatures of persistent foot-and-mouth disease virus (FMDV) infection to diagnostic markers and therapeutic control
Funding: ERA-NET ICRAD
This project coordinated by ANSES involves four other partners: the Friedrich-Loeffler-Institut (Germany), the Swedish University of Agricultural Sciences, Sciensano (Belgium) and the SAP Institute (Turkey). Its aim is to determine the molecular mechanisms that allow persistent FMDV infection to be established and maintained in ruminants, in order to improve diagnosis and develop therapeutic tools. More specifically, the project is seeking to:
- reveal alterations in the host response during persistent FMDV infection in ruminants;
- assess genes that are highly regulated during FMDV persistence as candidate host markers of persistent infection;
- identify pathways that could be targeted to prevent the establishment of FMDV persistence or stop the infection.
Hepatitis E virus: exposure and sharing dynamics in environments and livestock sectors
Funding: INRAE, SYALSA metaprogramme
The aim of this project is to bring together an interdisciplinary consortium of institutions (INRAE, CIRAD, ANSES, Inserm-UCPP) to study the exposure and sharing dynamics of the hepatitis E virus (HEV) in the environments and livestock sectors of Corsica, an HEV hyperendemic area. The project relies on a molecular epidemiology approach (analysis of the genotypic proximity of virus strains) and a series of approaches seeking to understand stakeholder practices (breeding, hunting, product processing and consumption practices).
Preparedness and response in an emergency context to pathogens of medical and veterinary importance
Funding: Franco-German call for projects (ANR)
Partners: Friedrich-Loeffler-Institut, Bernhard Nocht Institute for Tropical Medicine, GVB Unit of ANSES's Ploufragan Laboratory, University of Aix-Marseille
The general objective is to set up a portable sequencing and diagnostic platform that is capable of delivering critical information in a clinically relevant turnaround time at the start of an epidemic situation. The consortium is seeking to develop a standard protocol that could be applied on site using new-generation portable sequencing platforms (such as MinION) and sequence analysis software suites. Such software would be able to provide non-specialist users with information relevant to understanding the modes of transmission of infectious agents, the genomics of pathogens, and the evolution and possible origin of these infectious agents. Besides pathogen identification, the project will produce and validate easy-to-use detection tests that can be easily stored, transported and delivered to end-users and deployed in different possible epidemic scenarios. The PREPMedVet project brings together relevant French and German partners in both human and animal health, according to a One Health approach, and also involves end-users from the field in crisis situations.
Integrative pathobiology of tick-borne flaviviruses
Funding: French National Research Agency (AAPG2019)
Tick-borne encephalitis and louping ill are genetically related flaviviruses transmitted by ticks. They are responsible for encephalitis in humans and sheep respectively. The viruses' survival and replication depend on their ability to block the antiviral response and suppress cell functions, in particular through viral and cell protein interactions (PPIs), which disrupt the cell's protein interaction network (PIN). To understand the mechanisms of misappropriation of cell functions by viral proteins, the project aims to measure the impact of PPIs on viral replication, define the underlying molecular processes and assess their role in neuropathology. Disruption of the PIN in humans will also be addressed. This comparative study will provide information on the differences in the pathobiological traits of these two viruses, and more broadly of vector-borne viruses, in terms of host range, zoonotic potential and neurovirulence.
Cyclophilin inhibitors, broad-spectrum compounds for treating viral infections of the nervous system?
Funding: DIM1Health field of major interest
The project is seeking to identify broad-spectrum antiviral compounds for the treatment of viral infections of the nervous system. These compounds, in addition to allowing treatment of the huge number of infections known to date, will be of crucial importance when future threats emerge. The specific objectives are to screen a library of cyclophilin-inhibiting compounds for their antiviral potential in four disease models of nervous system infection (neuronal-glial cells infected with Zika, tick-borne meningoencephalitis, eastern equine encephalitis and SARS-CoV-2 viruses) in order to identify and select one or more compounds of interest.
The efficacy of these compounds will be tested on 3D in vitro infection models of the nervous system (minibrains) to understand their mechanism of action.
Antiviral strategies against three equine viruses, EVA, WNV and EHV-1: pharmaco-toxicological study of four candidate compounds in horses
The objective of the SAVE SATELLITE project is to conduct a pharmaco-toxicological study in horses of four compounds likely to be effective against three viral diseases: equine viral arteritis (EVA), West Nile virus (WNV) and equine rhinopneumonitis (EHV-1). This work is an essential preliminary step before conducting an efficacy study in animals, for which specific funding will be requested at a later stage. The results of this project will be important in determining whether contacts can be made with industry.
Identification of antiviral compounds for the treatment of equine viral encephalitis using an approach combining high-throughput imaging and neural cells derived from induced pluripotent stem cells.
The project's objectives are to develop a new model of infection of equine neural cells by the West Nile virus, to identify antiviral compounds using an unbiased screening approach and to characterise their mechanism of action.
Analysis of the transcriptome of human neural cells infected with tick-borne meningoencephalitis
The project's objective is to understand the modulations of the transcriptome (the set of all RNAs obtained from transcription of the genome) induced by tick-borne meningoencephalitis (TBEV) in human central nervous system cells. In particular, the aim is to identify cell signalling pathways involved in neuronal death, the innate immune response and virus replication.
COVID-19-related anosmia recovery
Funding: French National Research Agency (COVID-Resilience call)
The main objective of the project is to understand the cellular events leading to anosmia and patients' recovery. The golden Syrian hamster is being used as an animal model to test the efficacy of a treatment aimed at limiting the number of long-term anosmia cases in humans. Experimental infections of hamsters with SARS-CoV-2 are carried out at the UMR.
Molecular determinants governing flavivirus tropism, host range and virulence in France and Europe
The project studied the West Nile and Usutu viruses infecting humans and Equidae. The aim was to identify and compare the interactions between the proteins of the virus and those of the host, to help with the identification of key molecular determinants involved in the host range, zoonotic potential and neurovirulence of these two flaviviruses. Some determinants may represent molecular drivers of viral emergence.
Study of protein-protein interactions of equine infectious anaemia and African horse sickness viruses with their equine host
Funding: ANSES ("Cross-functional" calls for expressions of interest: inter-laboratories and other departments)
This project sought to perform protein-protein interaction (PPI) mapping for non-structural and accessory proteins of equine infectious anaemia virus (EIAV) and African horse sickness virus (AHSV) with their equine host using the yeast two-hybrid method. The aim was to identify the PPIs likely to be essential for the replication, persistence and/or spread of these viruses. Deciphering and characterising these virus-host molecular interactions opens up new prospects for predicting and simulating future emerging threats and developing effective countermeasures against these diseases, such as new broad-spectrum anti-infective compounds and attenuated strains for these pathogens.
Partners specific to the unit
In addition to collaborating with several partners common to the whole laboratory, the UMR has established specific partnerships with:
- The national reference centres for arboviruses (Marseille university hospital institute) and hepatitis E (Purpan university hospital, Toulouse)
- Animal Health Research Centre – National Institute for Agricultural and Food Research and Technology (CISA-INIA), Spain
- Italian health authority and research organisation for animal health and food safety (IZS), Italy
- Kimron Veterinary Institute, Israel
- London School of Hygiene and Tropical Medicine, UK
- National Veterinary Research Institute, Nigeria
- Pirbright Institute and Nottingham Veterinary School, UK
- Complutense University of Madrid, Spain
- University of Glasgow, UK
- University of Pretoria, South Africa
- Swedish University of Agricultural Sciences, Sweden
- Institute of Foot-and-mouth Disease (SAP), Turkey