How Bank Vole-PUUV Interactions Influence the Eco-Evolutionary Processes Driving Nephropathia Epidemica Epidemiology-An Experimental and Genomic Approach.

Philippe Marianneau,Sylvain Piry,Coralie Pulido,Johann Vulin,Guillaume Castel,Maxime Galan,Laure Benoit,Emmanuelle Artige,Sarah Madrières,Nicolas Leménager,Nathalie Charbonnel,Séverine Murri,Caroline Tatard,Anne Loiseau,Latifa Lakhdar

doi:10.3390/pathogens9100789

Abstract

In Europe, Puumala virus (PUUV) is responsible for nephropathia epidemica (NE), a mild form of hemorrhagic fever with renal syndrome (HFRS). Despite the presence of its reservoir, the bank vole, on most of French territory, the geographic distribution of NE cases is heterogeneous and NE endemic and non-endemic areas have been reported. In this study we analyzed whether bank vole-PUUV interactions could partly shape these epidemiological differences. We performed crossed-experimental infections using wild bank voles from French endemic (Ardennes) and non-endemic (Loiret) areas and two French PUUV strains isolated from these areas. The serological response and dynamics of PUUV infection were compared between the four cross-infection combinations. Due to logistical constraints, this study was based on a small number of animals. Based on this experimental design, we saw a stronger serological response and presence of PUUV in excretory organs (bladder) in bank voles infected with the PUUV endemic strain. Moreover, the within-host viral diversity in excretory organs seemed to be higher than in other non-excretory organs for the NE endemic cross-infection but not for the NE non-endemic cross-infection. Despite the small number of rodents included, our results showed that genetically different PUUV strains and in a lesser extent their interaction with sympatric bank voles, could affect virus replication and diversity. This could impact PUUV excretion/transmission between rodents and to humans and in turn at least partly shape NE epidemiology in France.

Highlights

Orthohantaviruses are considered emerging zoonotic pathogens [1] and represent a threat to Public Health [2] due to their wide distribution in the world, the diversity of their reservoirs [3] and Pathogens 2020, 9, 789; doi:10.3390/pathogens9100789 www.mdpi.com/journal/pathogensPathogens 2020, 9, 789 the lack of vaccines or treatments [4]
We focused on two French regions: a nephropathia epidemica (NE) endemic area (Ardennes) and a NE non-endemic area (Loiret), for which we recently isolated two French Puumala virus (PUUV) strains (Hargnies and Vouzon strains from Ardennes and Loiret, respectively) [42]
During the cross-experimental infections performed using wild bank voles (NE endemic, Ardennes; NE non-endemic, Loiret) and the two French PUUV strains isolated from these areas (NE endemic, Hargnies; NE non-endemic, Vouzon) (Figure 1), three bank voles died

Summary

Introduction

Orthohantaviruses are considered emerging zoonotic pathogens [1] and represent a threat to Public Health [2] due to their wide distribution in the world, the diversity of their reservoirs [3] and Pathogens 2020, 9, 789; doi:10.3390/pathogens9100789 www.mdpi.com/journal/pathogensPathogens 2020, 9, 789 the lack of vaccines or treatments [4]. In Europe, the most common orthohantavirus is Puumala virus (PUUV). It is carried by the bank vole (Myodes glareolus) [6], which is present all over the continent, except near the Mediterranean coast, the Iberian Peninsula and Greece [7]. In Europe, several thousand cases of NE are reported each year (European Center for Disease Prevention and Control), with a strong heterogeneity observed between countries. Over the last 10 years, a spatial expansion of NE cases outside of the endemic area has been observed in southern and western areas (National Reference Center for Hantavirus, [11]). We previously proposed to discriminate NE endemic areas (lots of NE cases, for example, Ardennes [12])

Objectives

Methods

Results