Detection and Genetic Characterization of Puumala Orthohantavirus S-Segment in Areas of France Non-Endemic for Nephropathia Epidemica.

Séverine Murri,Nicolas Leménager,Laure Benoit,Sylvain Piry,Sarah Madrières,Caroline Tatard,Nathalie Charbonnel,Philippe Marianneau,Julien Pradel,Emmanuelle Artige,Guillaume Castel,Philippe Audiot,Johann Vulin,Anne Loiseau,Sandra Lacôte

doi:10.3390/pathogens9090721

Abstract

Puumala virus (PUUV) in Europe causes nephropathia epidemica (NE), a mild form of hemorrhagic fever with renal syndrome (HFRS). The incidence of NE is highly heterogeneous spatially, whereas the geographic distribution of the wild reservoir of PUUV, the bank vole, is essentially homogeneous. Our understanding of the processes driving this heterogeneity remains incomplete due to gaps in knowledge. Little is known about the current distribution and genetic variation of PUUV in the areas outside the well-identified zones of NE endemicity. We trapped bank voles in four forests in French regions in which NE is considered non-endemic, but sporadic NE cases have been reported recently. We tested bank voles for anti-PUUV IgG and characterized the S segment sequences of PUUV from seropositive animals. Phylogenetic analyses revealed specific amino-acid signatures and genetic differences between PUUV circulating in non-endemic and nearby NE-endemic areas. We also showed, in temporal surveys, that the amino-acid sequences of PUUV had undergone fewer recent changes in areas non-endemic for NE than in endemic areas. The evolutionary history of the current French PUUV clusters was investigated by phylogeographic approaches, and the results were considered in the context of the history of French forests. Our findings highlight the need to monitor the circulation and genetics of PUUV in a larger array of bank vole populations, to improve our understanding of the risk of NE.

Highlights

Over the last two decades, since the advent of reliable tools for orthohantavirus infection diagnosis, the human diseases associated with these zoonotic viruses have increasingly been recognized as a growing public health concern worldwide
We investigated whether Puumala virus (PUUV) circulates in bank vole populations from French geographic areas in which the presence of this virus had never been tested, but in which its circulation was considered likely, due to proximity to areas of nephropathia epidemica (NE) endemicity or the detection of recent human cases in nearby areas
We provide the first evidence of PUUV circulation in bank vole populations from one French area currently considered to be non-endemic for NE: the southern Morvan forest

Summary

Introduction

Over the last two decades, since the advent of reliable tools for orthohantavirus infection diagnosis, the human diseases associated with these zoonotic viruses have increasingly been recognized as a growing public health concern worldwide. In Europe, most human cases are caused by the Puumala virus (PUUV) [1]. PUUV is transmitted to humans via aerosols contaminated with the excreta of its sole, specific natural reservoir, the bank vole, Myodes glareolus, a forest-dwelling rodent species [5]. Previous studies [6,7,8] have suggested that PUUV transmission is entirely horizontal in bank vole populations, through direct contact between individuals or indirect contamination via contact with infected feces or urine in the environment [7,9]. In areas of PUUV endemicity, the virus circulates in both the reservoir and human populations.

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Conclusion