Published on December 10, 2018 | Updated on December 11, 2018

H-LIKE Project

Eco-infectiology of HBV-like viruses: assessment of cross-species transmission

Leaders: Dominique Pontier (LBBE) and François-Loïc Cosset (CIRI)

Hepatitis B is a major health problem affecting 350 million people worldwide, which represents a substantial economical and health burden with approximately 0.6-1 million deaths occurring each year as a result of HBV infection. HBV belongs to the Orthohepadnavirus genus of the Hepadnaviridae family, for which it is the only human representative. Some HBV-like viruses have been discovered in other mammals (woodchuck, ground squirrel and non-human primates) but to date, no cross species transmission events have been confirmed. Strikingly, since the advent of extensive sequencing, three novel HBV-like viruses’ sequences have been found in different bat species in Central America and Africa. This introduces a new element to be considered in the natural history and origin of this virus, which remains unresolved, giving rise to the hypothesis that bats may be the natural reservoir for HBV and sources of zoonotic transmission. However, only 54 species of bats - representing less than 5% of the total number of existing bat species - have been screened so far, suggesting that there is potentially a larger diversity of viruses yet to be discovered, which may change the current picture of HBV evolution.
In this Ecofect project, we aim to (i) identify new HBV-like viruses in bats living in different habitat conditions from South America, Africa and Europe, (ii) characterize the phylogenetic relationships with the other reported HBV viruses and (iii) describe patterns of viral circulation both intra- and inter-species, and (iv) characterize the molecular cell entry determinants of HBV-like compared to the human HBV from a mechanistic perspective. We will focus on HBVlike viruses found in bats to understand whether and how the HBV-like virus envelope glycoproteins play a role in the potential crossing of the interspecies barrier. Bioinformatics analyzes will be carried out on HBV and HBV-like viruses sequences to identify coevolution clusters in core and surface proteins of these viruses, which could mark molecular determinants involved in cell entry processes of HBV and HBV-like viruses. This will allow experimental characterization of the molecular cell entry determinants of HBV-like compared to the human HBV thanks to construction of HDVHBV and HDVHBV-like pseudo-viral particles.
Finally, all data generated from the ecological and molecular parts will be integrated in a
mathematical model to test hypotheses on ecological and evolutionary factors potentially shaping virus host specificity and cross-species transmission. Taken together, the expected results should bring innovative insights into the zoonotic potential of bat hepadnaviruses. The present proposal will generate a wide range of empirical and theoretical results, as well as methodological developments, which could be valuable for a large range of host-pathogen systems.

Dominique Pontier, team "Ecoépidémiologie évolutionniste" (LBBE) and François-Loïc Cosset, team "Virus à enveloppes, vecteurs et immuno-thérapie" (CIRI).
Collaborative partners: Barthélémy Ngoubangoye, Franceville International Center for Primatology (CIRMF) in Gabon, Guy Perrière, team "Bioinformatique, Phylogénie et Génomique Évolutive" (LBBE),  Nathalie Charbonnel, INRA Montpellier,  Alessandra Carbone du Computational and Quantitative Biology of Paris and Christophe Combet (CRCL Lyon).
Project duration:
3 years
Financing :
Post-doc fellowship and consumable money
Post-doctoral fellow:
Jimena Perez-Vargas