Research Projects - Axis 2 (PI: L. Etienne)

Axis 2 (PI: Lucie ETIENNE): Evolution of virus-host interactions, and impact on cross-species transmissions

Viruses interact with many cellular proteins, being pro- or anti-viral. Because viruses have been evolving with their host over millions of years, their evolutionary histories include virus-host species coevolution, as well as cross-species transmission events.

Hosts and pathogenic viruses are locked in an “evolutionary arms-race” (or “genetic conflict”), in which they coevolve to overcome the other and survive. Viruses are major drivers of mammalian adaptation. This notably led to rapid evolution and signatures of adaptation (positive selection) at the interface that has been important in vivo and over time.

Viruses are adapted to their natural host species. However, due to the species-specificity of virus-host interactions, (i) our cellular proteins may be efficient barriers against viral spillovers and (ii) natural variants in other species may be antivirals against human pathogens.

In our research program, we are broadly interested in better characterizing virus-host interfaces and their coevolution. The ultimate goals are to better understand the barriers against current pathogens and emerging viruses, as well as to identify novel targets for antiviral prevention or cure.

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Approaches: We use a combination of phylogenetics, evolutionary analyses of host and viral genomes, as well as cellular and molecular biology and virology.

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Evolutionary & functional characterization of host genes influencing primate lentivirus/HIV replication.

Lentiviruses have coevolved with primates over millions of years, with a mix of coevolution and spillovers, including the cross-species transmissions at the origin of HIV/AIDS in human.

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  We have developed the DGINN pipeline to Detect Genetic INNovations on protein-coding genes (Picard et al. Nucleic Acids Research 2020, publicly available at GitHub). DGINN automates, from a gene name/sequence, the search for homologs in databases, identification of orthologs and paralogs, recombination, and positive selection using five methods. We validated DGINN on 19 primate genes with known evolutionary histories and made some new discoveries along the way! Incollaboration with Laurent Guéguen (LBBE, Lyon), we continue to enrich & update DGINN. -send us your comments!

• We are now using DGINN to characterize the evolutionary history of primate interferon-stimulated genes (ISGs). On the genes with the strongest signatures of adaptation, we perform genetic manipulations and ectopic expression in primate cells to identify the genes influencing the replication of HIV and other primate lentiviruses. Here, we aim to identify and characterize new evolutionarily-relevant HIV-cell interfaces.

(Recent work at: Chougui et al Nature Microbiol 2018 -collab. with Margottin-Goguet Lab, Institut Cochin)

Ancient and modern coevolution between bats and viruses

Bats harbor a high number of viruses, but they appear asymptomatic to most viral infections that are pathogenic to other mammals. It seems that they have evolved a unique balance between immune antiviral defense and viral tolerance. However, most of bat immune evolutionary and functional history remains unknown. Here, we aim to decipher how bat’s immunity has adapted to long-term association with diverse viruses and to determine if modern viruses induce a fitness cost on bats.

• Specifically, we characterize the evolutionary and functional diversification of antiviral effectors in bats, in which we found genomic and molecular adaptations. We also hope to bring insights on the genetic determinants of host species-specificity, which partly contribute to current and future epidemics.

(Recent work at: Jacquet et al Frontiers Immunol 2020, Jacquet et al JVI 2018 ).

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We have job openings!
https://ciri.ens-lyon.fr/teams/lp2l/job-openings-in-the-lab/funded-phd-student-postdocs-openings

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Funding (in alphabetical order):
amfAR, ANR, ANRS, CNRS, FINOVI, FRM, JoRISS, LabEx ECOFECT, Région Auvergne Rhône Alpes, Sidaction

Alumni:

2016-2020 - Léa Picard, PhD student, ENS-Lyon. Comentored with L. Guéguen. Now, Postdoc @ Tadashi Yamamoto Lab, Okinawa, Japan.
2020 - Clément Verez, Undergraduate student, IUT, Université Lyon 1. Now, Student @ ENS-Lyon.
2019 - Margaux Pillon, Master-degree student, M2 "Infectiologie", UCBL. Now, PhD student @ UCBL.
2019 - Manon Picquenot, Master-degree student, M2 "Biodiversité, Ecologie et Evolution", UCBL.
2015-2019 - Mégane Wcislo, Graduate student, UCBL and ENS Lyon.
2016-18 - Fabien Filleton, Ingénieur de Recherche. Now, Engineer.
2017-18 - Ariel De Bernardo, Assistant Ingénieur. After, Ingénieur d'Etude @ CRCL Lyon.
2016 - Nina Courault, Master-degree student, University of Tours.
2014 - From the Emerman Lab: Rossana Colon-Thillet, Prep Student, University of Washington. After, PhD student in the Malik Lab @ Fred Hutch, Seattle WA, USA.