Virology UMR

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

Funding: IFCE

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.

Funding: INRAE

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

Funding: INRAE

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

Funding: INRAE

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.