Published on December 11, 2018 | Updated on December 11, 2018


A multiscale approach to decipher evolutionary determinants regulating cross-species transmission of bat’s viruses

Coordinator : Patrice André (CIRI) - Ecofect partners : Dominique Pontier (LBBE) , François-Loïc Cosset (CIRI), Lucie Etienne (CIRI), Anja Böckmann (MMSB), Laurent Guéguen (LBBE)

Emerging infectious diseases represent a major threat for public health, biodiversity and global economies. In humans, the global burden of emerging and re-emerging infections already exceeds 300 million disability-adjusted life years (DALYs) (OMS 2011). Animals, and in particular wildlife, are the most likely sources of emerging infectious diseases threatening human populations, with >70% of emerging events being caused by zoonotic pathogens. Whereas information exists on human and commensal rendering control measures possible, little is known on non-human, non-agricultural systems.
There is an increasingly growing interest in bats, one of the most diverse and ancient mammalian order, as significant sources of zoonotic diseases impacting public health. Bats host more (zoonotic) viruses per species than any other mammal species, and in many cases the viruses bats carry do not appear to have major impact on the health of the bats. Many aspects of the interactions between bats and viruses remain a mystery. Basic immunological commonalities are shared among all mammals and could restrict both the pathogenicity and cross species barrier between bats species and between bats and primates. In addition, certain unique life history (e.g., long life span given their body size, many species can roost in the same site), physiological (e.g., high metabolism due to flight) and immunological traits peculiar to bats may help to explain the plethora of agents associated with this mammalian order and the species restriction.
Hepadnaviridae are ancient pathogens that might have evolved first in bats and show the highest diversity in this group, before spreading to other taxonomic groups, including human. Hepatitis B virus (HBV) is a model of a virus that is an expert in evading immune response and to pervert the host metabolism; two features that might contribute to establish chronic infection. A better understanding of HBV and HBV-like natural history and co-evolution within their natural hosts is for instance of major interest not only to fundamental virology but also to better understand the host immune functions and metabolic pathways dependence that are essential in the virus biology.
The METINBAT project aims to (i) determine the evolution and diversity of bat’s antiviral genes to uncover potential genetic conflicts with pathogenic viruses and the impact of different life styles; (ii) link this diversity (as translated into amino acid variations) to the structural determinants of HBV cell entry and understand how species variations could have impact on cross-species transmission; (iii) investigate the interplay between hepadnavirus infection and metabolism by studying the host metabolic nuclear factors impact on hepadnavirus genomic regulatory regions.

CoordinatorPatrice André, team "Biologie cellulaire des infections virales" (CIRI).
Ecofect partners : Dominique Pontier, team "Ecoépidémiologie Evolutionniste" (LBBE), François-Loïc Cosset, team "Virus Enveloppés, Vecteurs et Immunothérapie" (CIRI), Lucie Etienne, team "Interaction Hôte-Pathogène lors de l’Infection Lentivirale" (CIRI), Anja Böckmann, team "Protein Solid State NMR" (MMSB), and Laurent Guéguen, team "Bioinformatique, Phylogénie et Génomique Evolutive" (LBBE).
Project duration : 3 years
Financing :
PhD and Post-doc fellowships and consumable money
PhD fellows :
Karim Mouzannar, Camille Ménard
Post-doctoral fellows : Stéphanie Jacquet, Marie Dujardin