Stéphan ZIENTARA
Joint Research Unit Virology 1161 ANSES/INRA/ENVA
23 Avenue du Général de Gaulle, Maisons-Alfort
 
Research area of the Unit
 
The JRU (Joint Research Unit) Virology is a trans-institutional research unit dedicated to animal and veterinary public health, an alliance between ANSES, INRA and the French veterinary school in Alfort.
We investigate animal viruses responsible for epizootics or with potential for zoonotic transmission and/or emergence. We thus i) characterise viral diversity, interspecies transmission of virus, viral pathogenesis and immune responses elicited by viral infection, and notably to instruct risk evaluation and decision making, ii) develop new diagnostic methods optimised for epidemiological surveillance and phylogeny, and in particular for viruses responsible for foot and mouth disease, bluetongue, hepatitis E and equine diseases such as West Nile fever and iii) develop new vaccination strategies based on recombinant DNA technologies.
To gain understanding of interspecies viral transmission, the JRU compares viral strains circulating in humans and animals and defines virus/host interactions promoting or limiting cross-species transmission. Viruses such as hepatitis E virus (HEV), West Nile virus (WNV), encephalomyocarditis virus, coronaviruses, Schmallenberg virus (SBV), and borna disease virus (BDV) are studied in this regard.
 
Contribution to the programme
 
The JRU will investigate the molecular mechanisms by which pathogens cross the species barrier. Several potential zoonotic agents (BDV, HEV, WNV, EMC, SBV, BTV, coronaviruses) will be investigated. Projects to be initiated are as follows
- Identification of HEV virulence factors and molecular determinants of cross-species transmission. The cellular partners and signalisation pathways activated during the viral cycle will be identified in primary cells, in order to facilitate design of genetically modified cell lines permissive to viral growth. Viral mutants will then be used to characterise cellular and molecular mechanisms involved in HEV multiplication in pig and human hepatocytes, thus contributing to the identification of viral determinants involved in virulence and cross-species infections.
– Role of orbivirus proteins in innate immunity and host specificity. NS3, a non-structural protein of BTV, plays an important role in viral morphogenesis and pathogenesis. Novel NS3 binding partners will be identified using a yeast two-hybrid screen and cDNA libraries from different species. These different approaches will provide new insight into the physiopathology of orbiviral infections and the mechanisms evolved by these viruses to counteract the antiviral response and cross the species barrier.
Viruses other than those already studied at the JRU could also represent good candidates to investigate mechanisms involved in cross-species barrier.
 
References over the past 5 years
  1. Bouquet J, Tessé S, Lunazzi A, Eloit M, Rose N, Nicand E, Pavio N. Close similarity between sequences of hepatitis E virus recovered from humans and swine, France, 2008-2009. Emerg Infect Dis. 2011 Nov;17(11):2018-25.
  2. Renou C, Cadranel JF, Bourlière M, Halfon P, Ouzan D, Rifflet H, Carenco P, Harafa A, Bertrand JJ, Boutrouille A, Muller P, Igual JP, Decoppet A, Eloit M, Pavio N. Possible zoonotic transmission of hepatitis E from pet pig to its owner. Emerg Infect Dis. 2007 Jul;13(7):1094-6.
  3. Carocci M, Cordonnier N, Huet H, Romey A, Relmy A, Gorna K, Blaise-Boisseau S, Zientara S, Kassimi LB. Encephalomyocarditis virus 2A protein is required for viral pathogenesis and inhibition of apoptosis. J Virol. 2011 Oct;85(20):10741-54. Epub 2011 Aug 17.
  4. Hemati B, Contreras V, Urien C, Bonneau M, Takamatsu HH, Mertens PP, Bréard E, Sailleau C, Zientara S, Schwartz-Cornil I. Bluetongue virus targets conventional dendritic cells in skin lymph. J Virol. 2009 Sep;83(17):8789-99. Epub 2009 Jun 24.
  5. Bréard E, Belbis G, Hamers C, Moulin V, Lilin T, Moreau F, Millemann Y, Montange C, Sailleau C, Durand B, Desprat A, Viarouge C, Hoffmann B, de Smit H, Goutebroze S, Hudelet P, Zientara S. Evaluation of humoral response and protective efficacy of two inactivated vaccines against bluetongue virus after vaccination of goats. Vaccine. 2011 Mar 16;29(13):2495-502. Epub 2011 Jan 21.
  6. Brnic D, Stevanovic V, Cochet M, Agier C, Richardson J, Montero-Menei CN, Milhavet O, Eloit M, Coulpier M. J Virol. Borna disease virus infects human neural progenitor cells and impairs neurogenesis.2012 Mar;86(5):2512-22. Epub 2011 Dec 21.
  7. Guy M, Chilmonczyk S, Crucière C, Eloit M, Bakkali-Kassimi L.Efficient infection of buffalo rat liver-resistant cells by encephalomyocarditis virus requires binding to cell surface sialic acids. J Gen Virol. 2009 Jan;90(Pt 1):187-96.