Stage M2: Endogenous ß-retroviruses diversity in small ruminants.

 Stage · Stage M2  · 6 mois    Bac+5 / Master   UMR754-Infections Virales et Pathologie Comparée & Prabi-amsb · Lyon (France)

Mots-Clés

Endogneous Retroviruses Polymorphism Genomic Transcriptomic Small Ruminants

Description

Retroviridae is a large family of RNA viruses infecting humans and animals responsible for a variety of diseases such as severe immunodeficiency like AIDS in humans, or cancers. Retroviruses are also major components of the mammalian genomes. Referred as endogenous retroviruses (ERV), they result from ancient integrations of exogenous infectious retroviruses into the germ cells. Approximately 8% of our human genomes is made of endogenous retroviral sequences. They have long been considered as "junk DNA" but it is now well established that they participated to the genome evolution and even carry indispensable functions for the mammalian life and development. Most ERVs in their host genomes are originated from now extinct exogenous retroviruses. Still, a few species have been described, displaying at the same time ERVs and the circulating exogenous homologous virus in their host. Among them, the small ruminants genomes carry multiple ERV copies of γ-retroviruses but also of ß- retroviruses. These last ones co-exist with their exogenous counterparts, namely JSRV (Jaagsiekte sheep retrovirus) and ENTV (Enzootic Nasal Tumor Virus). JSRV and ENTV are oncogenic viruses responsible for respectively pulmonary adenocarcinoma and nasal adenocarcinoma in sheep and goats. Up to day, no oncogenic role has been associated to ERVs, on the contrary they may protect their host from their exogenous counterparts by blocking the entry or the release of virions but their biological functions are not fully known. These ß-ERVs are polymorphic both in terms of sequences and of the DNA region they integrated in along the host genome, suggesting that the endogenization process may be still ongoing. The main objective of this project will be to characterize the polymorphism of the ß-ERVs in their host genome and dissect the expression and diversity of the ß-ERVs in sheep. The project will rely on the analysis of omics data (RNA and DNA-Seq) and subdivided into 2 parts: 

  • Mapping of ß-ERVs within the reference genome (Benz2616; Salavati et al 2020). ERVs’ polymorphism (integration loci and sequences) will be determined by combining the analysis of Whole Genome Sequencing data (available) and targeted sequencing (Long read and short read sequencing, in process).
  • Body wide ERVs’ transcription regulation and diversity. Tissues and ERV specific signatures will be characterized in 58 different tissues (mRNA-Seq data available) isolated from the reference sheep (Benz2616).

Overall this project will offer a comprehensive atlas of ERVs integration signatures and expression repertoire in sheep. It will help us to decipher their biological functions, how they shaped the sheep genome and will be a milestone to study their interplay with their exogenous counterpart.


Bibliography

Arnaud, F., Murcia, P. R., & Palmarini, M. (2007). Mechanisms of late restriction induced by an endogenous retrovirus. Journal of Virology, 81(20), 11441–11451. https://doi.org/10.1128/JVI.01214-07

Artesi, M., Hahaut, V., Cole, B., Lambrechts, L., Ashrafi, F., Marçais, A., Hermine, O., Griebel, P., Arsic, N., van der Meer, F., Burny, A., Bron, D., Bianchi, E., Delvenne, P., Bours, V., Charlier, C., Georges, M., Vandekerckhove, L., Van den Broeke, A., & Durkin, K. (2021). PCIP-seq: simultaneous sequencing of integrated viral genomes and their insertion sites with long reads. Genome Biology, 22(1), 97. https://doi.org/10.1186/s13059-021-02307-0

Chiu, E. S., & VandeWoude, S. (2021). Endogenous Retroviruses Drive Resistance and Promotion of Exogenous Retroviral Homologs. Annual Review of Animal Biosciences, 9(1), 225–248. https://doi.org/10.1146/annurev-animal-050620-101416 Cumer, T., Pompanon, F., & Boyer, F. (2019). Old origin of a protective endogenous retrovirus (enJSRV) in the Ovis genus. Heredity, 122(2), 187–194. https://doi.org/10.1038/s41437-018-0112-z

Monot, M., Archer, F., Gomes, M., Mornex, J.-F., & Leroux, C. (2015). Advances in the study of transmissible respiratory tumours in small ruminants. Veterinary Microbiology, 181(1–2), 170–177. https://doi.org/10.1016/j.vetmic.2015.08.008

Salavati, M., Caulton, A., Clark, R., Gazova, I., Smith, T. P. L. Worley, K. C., Cockett, N. E., Archibald, A. L., Clarke, S. M., Murdoch, B. M., & Clark, E. L. (2020). Global Analysis of Transcription Start Sites in the New Ovine Reference Genome (Oar rambouillet v1.0) . In Frontiers in Genetics (Vol. 11, p. 1184). https://www.frontiersin.org/article/10.3389/fgene.2020.580580 

Candidature

Procédure : Envoyer un mail de candidature avec CV et motivation à Jocelyn Turpin (jocelyn.turpin@univ-lyon1.fr) & Vincent Navratil (vincent.navratil@univ-lyon1.fr)

Date limite : None

Contacts

Jocelyn Turpin

 joNOSPAMcelyn.turpin@univ-lyon1.fr

Offre publiée le 14 septembre 2021, affichage jusqu'au 7 novembre 2021