PhD Puumala, Hantavirus & Bank voles, Montpellier, France

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*PhD Title:* Importance of the inflammatory immune response in the spatial distribution of Puumala hantavirus in French and European populations of its hosts, the bank vole /Myodes glareolus/

*Supervisor 1: *N Charbonnel - INRA Montferrier sur Lez (nathalie.charbonnel@supagro.inra.fr)

**Supervisor* 2:* P Marianneau - ANSES Lyon (philippe.marianneau@anses.fr)

*Funding* :½ INRA-EFPA + ½ ANSES

*Themes : *Genomic architecture of bank vole tolerance/resistance to hantavirus, immunogenetics, evolution of the inflammatory immune response, emerging zoonoses

*Detailed summary : *

Nephropathia epidemica (NE) is a mild form of hemorrhagic fever with renal syndrome (HFRS) caused by the hantavirus Puumala (PUUV). In Europe, its distribution is fragmented, whereas the bank vole Myodes glareolus, which is the reservoir of PUUV, is common all over the continent. Determining the causes underlying this heterogeneity is of main importance to better understand and prevent the risks of NE emergence. Besides climatic and ecological hypotheses, we have proposed that the geographic variability of bank vole immune responses to PUUV infection could shape differences in PUUV prevalence, and consequently NE incidence.

In this context, this PhD thesis will aim at 1) investigating experimentally M. glareolus tolerance to PUUV, 2) identifying the genomic regions evolving under PUUV mediated selection and therefore potentially associated with tolerance mechanisms, and 3) analysing the impact of helminth infection on M. glareolus sensibility to PUUV.

_Question 1 : Tolerance to PUUV and inflammatory response_

i) We will test the assumption that in NE endemic areas, M. glareolus is more tolerant to PUUV: viral loads are higher, and for a given viral load, the impact on M. glareolus fitness is lower than in non endemic areas.
ii) We will investigate whether regulation of inflammatory response underlies this tolerance. A higher inflammatory response is expected in PUUV endemic areas than in non endemic ones.

_Question 2 – Genome scans _

i) We will analyse the genetic bases of M. glareolus adaptation to PUUV
ii) This adaptation evolves in heterogeneous landscapes at large geographic scales (Temperate vs boréal areas) and fine ones (resources, prédation, pathobiome strongly vary between localities) We therefore
expect different signatures of sélection along transect ranging from PUUV endemic to non endemic areas. Genome scans should allow the detection of such signatures. We have previously leaded such analyses
using localities from the French Ardennes using RAD sequencing. During this PhD thesis, the candidate will study other transects in France (Jura-Ain) and Scandinavia (Finland, Sweden).

_Question 3 – PUUV-helminth coinfection and inflammatory response_

i) We will test the hypothesis that the nematode Heligmosomum mixtum makes infection by PUUV easier.
ii) We assume that H. mixtum infection leads to a modification of immune trade offs between Th1/Th2/Th17 pathways, in favour of Th2. We will investigate this question using expérimental coïnfections and longitudinal surveys conducted in Finland.

*Candidates*:

The successful applicant will be broadly trained in evolutionary ecology or virology, and he should be interested by genomic and experimental approaches in the context of host pathogen interaction studies. He/she must have expertise in one or more of the following areas: rodent sampling, molecular biology, NGS, bioinformatics, experimental infections.

To apply, please submit a cover letter describing your research interests, a CV, and the names and contact information for references to both supervisors. Deadline for application is May 31, 2013. A short-list of candidates will be interviewed by N. Charbonnel and P. Marianneau, until the position is filled.

More information is available on the following website, CBGP lab : http://www.sibaghe.univ-montp2.fr/futur-doctorant/candidature/sujets-de-theses**