Contributors: Centre collaborateur de l'OMS - Rage / World Health Organization Collaboration Centres - Rabies (CC-OMS / WHO-CC); Institut Pasteur Paris (IP)-Organisation Mondiale de la Santé / World Health Organization Office Genève, Suisse (OMS / WHO); The University of Sydney; Laboratoire de la rage et de la faune sauvage de Nancy (LRFSN); Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES); Génomique (Plate-Forme) - Genomics Platform; Institut Pasteur Paris (IP); This work was supported by European Union Seventh Framework Programme PREDEMICS (grant number 278433) and by the Agence Nationale de la Recherche (grant number BSV3-0019). The Genomics Platform is member of ªFrance Génomiqueº consortium (ANR10-INBS- 09-08). HB, LD and EB were supported by the European Virus Archive goes Global (EVAg) project that has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No 653316. ECH is funded by an ARC Australian Laureate Fellowship (FL170100022).; We are grateful to Karine Reynaud from the Unit Biology of Development and Reproduction of the Ecole Nationale Vétérinaire d'Alfort for providing the dog embryos, and to Benoît Combe of the Entente de Lutte Interdépartementale contre les Zoonoses of Malzeville for his help in obtaining fox embryos. We also thank Laurence Ma and Magali Tichit from the Genomics Platform for technical assistance with NGS sequencing.; ANR-12-BSV3-0019,Viva&host,Variabilité génétique au sein des populations de virus à ARN négatif non segmenté et adaptation à l'hôte(2012); ANR-10-INBS-0009,France Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010); European Project: 278433,EC:FP7:HEALTH,FP7-HEALTH-2011-two-stage,PREDEMICS(2011); European Project: 653316,H2020,H2020-INFRAIA-2014-2015,EVAg(2015)
نبذة مختصرة : International audience ; The development of high-throughput genome sequencing enables accurate measurements of levels of sub-consensus intra-host virus genetic diversity and analysis of the role played by natural selection during cross-species transmission. We analysed the natural and experimental evolution of rabies virus (RABV), an important example of a virus that is able to make multiple host jumps. In particular, we (i) analyzed RABV evolution during experimental host switching with the goal of identifying possible genetic markers of host adaptation, (ii) compared the mutational changes observed during passage with those observed in natura, and (iii) determined whether the colonization of new hosts or tissues requires adaptive evolution in the virus. To address these aims, animal infection models (dog and fox) and primary cell culture models (embryo brain cells of dog and fox) were developed and viral variation was studied in detail through deep genome sequencing. Our analysis revealed a strong unidirectional host evolutionary effect, as dog-adapted rabies virus was able to replicate in fox and fox cells relatively easily, while dogs or neuronal dog cells were not easily susceptible to fox adapted-RABV. This suggests that dog RABV may be able to adapt to some hosts more easily than other host variants, or that when RABV switched from dogs to red foxes it lost its ability to adapt easily to other species. Although no difference in patterns of mutation variation between different host organs was observed, mutations were common following both in vitro and in vivo passage. However, only a small number of these mutations also appeared in natura, suggesting that adaptation during successful cross-species virus transmission is a complex, multifactorial evolutionary process.
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