The ZEN team (Equine Zoonoses and NeuroVirology) studies flavivirus, bornavirus and alphavirus virulence. Those viruses are emerging and re-emerging zoonotic neurotropic viruses of medical and veterinary significance. The ZEN team is divided in two groups working cohesively and collaboratively to ensure a comprehensive understanding of the pathobiology and epidemiology of these viruses, to develop new diagnostic tools, and to identify potential therapeutic or preventive strategies.

Currently, three Flaviviruses and one Alphavirus constitute the main research targets: West Nile Virus (WNV), USUTU Virus (USUV), tick-borne-encephalitis virus (TBEV) and the Eastern equine encephalitis virus (EEEV). In France, and throughout Europe, WNV is a recurrent sanitary problem. Its close relative, USUV has rapidly spread through the French territory over the past few years, causing bird mortalities and occasional human and equine neurological diseases. TBEV is transmitted to animals and humans via tick bites, but it can also be found in goat milk and several outbreaks of TBEV infections can be caused by the consumption of unpasteurized goat dairy products. EEEV is an alphavirus which is also responsible for neurological diseases in human and horses. It is currently restricted to America.

Our missions:

As European Reference Laboratory (EURL) for Equine diseases, ZEN has the mission to ensure the high quality, uniform, and reliable the testing of West Nile Virus and Equine Viral Encephalitis (Eastern, Western and Venezuelan equine encephallomyelitis) carried out by all the European national reference laboratories (NRL) in the network. Trainings sessions are provided as needed to researchers throughout Europe. We also develop methods that are then transferred to the accredited laboratories. Finally, once a year, ZEN organizes a workshop to discuss results of National Reference Laboratory analyses, and provide advices and ways of improvements.

Link to the EURL Website: https://eurl-equinediseases.anses.fr

As National Reference Laboratory (NRL), ZEN has the mission to ensure the diagnostic of African Horse sickness (AHS), West Nile Fever (and other emerging flaviviruses), and Equine Viral Encephalitis. Most of these viruses have an enzootic cycle and are zoonotic and neurotropic in equine and humans. ZEN is at the head of a network of 7 laboratories located across the country. To that extent, we have to confirm results coming from this network and to continuously develop better diagnostic tools, that guarantee faster and more reliable results.

Rapid risk assessment: Following outbreaks, ZEN rapidly develops new tools, methodologies and research projects in order to fill knowledge gaps on emerging viruses pathobiology and epidemiology to allow the Agency to assess the resulting risk of exposure. Expert team members also share their expertise through on-going discussions with ANSES experts committees providing risk assessments in animal health and welfare and in food biological safety.

Research axes:

Nolwenn’s group – Virus ecology and evolution

- Epidemiology. We develop national surveillance programs to track virus geographic distribution and identify the anthropogenic and environmental factors that contribute to disease emergence and spread.

- Evolution. We use next generation sequencing approaches to discover and characterize novel viruses, and to track virus evolution overtime, thus identifying ecological determinants of virus cross-species transmission and dispersion.

- Characterize viruses’ transmission cycles. We assess host exposure through field studies using both wild and captive animals. We also evaluate host competency and virus transmission modes through experimental infections.

- Viral determinants of pathogenicity, transmission and virulence. We use a combination of in vitro and in vivo experiments to assess differences in the pathogenicity and transmission of different viral strains and species. The viral molecular determinants of differences are characterized through a combination of interatomic (Y2H), proteomics, and transcriptomics. Finally, chimeric and mutant viruses are engineered to confirm the role of specific genomic regions.

- Identification of antiviral molecules. The group has develop an in vitro technique based on Xcelligence to screen for antiviral molecules and employs in vivo approaches to test the toxicity of identified molecules in equine.

- Role of other parasites in host susceptibility to viruses. We use a combination of field studies and in vivo experiments to test the role of the microbiome, and the impact of co-infection with other organisms (bacteria, viruses, parasites) on host immune response to infection, and virus pathogenicity, transmission, and evolution.

Muriel’s group – Neuropathology and antivirals

- Understand neuropathogenicity. We use human and equine primary-type cell culture - 2D and 3D (cerebral organoids) cultures of the central nervous system derived from fetal neural progenitor cells or induced pluripotent stem cells – to address the mechanisms by which neurotropic viruses damage the human and equine brains. The role of cell-type specific immune response as well as cellular factors involved in neuronal death and viral replication in the brain are investigated.  

- Search for antiviral therapies.  Our goal is to identify antiviral molecules that prevent the replication of Flavivirus and Alphavirus in the human and equine brains as well as to unravel their mechanism of action. To this aim, we use recently developed screens and tests of high predictive value (based on 2D/3D-human and equine primary-type neural cells and image analysis

Our members :

• Head :

Muriel Coulpier (INRAE)

Nolwenn M Dheilly (ANSES)

•  Scientific Staff :

Gaëlle Gonzalez (ANSES, head of WNV NRL)

Camille Migne (ANSES)

• Technical and Administrative Staff : 

Rayane Amaral Moraes (ANSES)

Marielle Cochet (AI, INRAE)

Marine Dumarest (ANSES)

Kamila Gorna (Tech, ANSES)

François Piumi (IE, INRAE)

• Postdoctoral Researcher :

Noémie Berry (INRAE)

• PhD Candidate : 

Lise Fiacre (ANSES/CIRAD), Marielle Cochet (INRAE)

• Temporary Staff :

Valentine Chaillot (Master Student)

Aicha Dembele (Tech, INRAE)