Molecular Epidemiology and Evolution of European Bat Lyssavirus 2

Abstract

Bat rabies cases in Europe are mainly attributed to two lyssaviruses, namely European Bat Lyssavirus 1 (EBLV-1) and European Bat Lyssavirus 2 (EBLV-2). Prior to the death of a bat worker in Finland in 1985, very few bat rabies cases were reported. Enhanced surveillance in the two subsequent years (1986–1987) identified 263 cases (more than a fifth of all reported cases to date). Between 1977 and 2016, 1183 cases of bat rabies were reported, with the vast majority (>97%) being attributed to EBLV-1. In contrast, there have been only 39 suspected cases of EBLV-2, of which 34 have been confirmed by virus typing and presently restricted to just two bat species; Myotis daubentonii and Myotis dasycneme. The limited number of EBLV-2 cases in Europe prompted the establishment of a network of European reference laboratories to collate all available viruses and data. Despite the relatively low number of EBLV-2 cases, a large amount of anomalous data has been published in the scientific literature, which we have here reviewed and clarified. In this review, 29 EBLV-2 full genome sequences have been analysed to further our understanding of the diversity and molecular evolution of EBLV-2 in Europe. Analysis of the 29 complete EBLV-2 genome sequences clearly corroborated geographical relationships with all EBLV-2 sequences clustering at the country level irrespective of the gene studied. Further geographical clustering was also observed at a local level. There are high levels of homogeneity within the EBLV-2 species with nucleotide identities ranging from 95.5–100% and amino acid identities between 98.7% and 100%, despite the widespread distribution of the isolates both geographically and chronologically. The mean substitution rate for EBLV-2 across the five concatenated genes was 1.65 × 10−5, and evolutionary clock analysis confirms the slow evolution of EBLV-2 both between and within countries in Europe. This is further supported by the first detailed EBLV-2 intra-roost genomic analysis whereby a relatively high sequence homogeneity was found across the genomes of three EBLV-2 isolates obtained several years apart (2007, 2008, and 2014) from M. daubentonii at the same site (Stokesay Castle, Shropshire, UK).

Serological Survey of Lyssaviruses in Polish Bats in the Frame of Passive Rabies Surveillance Using an Enzyme-Linked Immunosorbent Assay

“…Daubenton's bat (Myotis daubentonii) is the main reservoir of EBLV-2 [4], and EBLV-2 cases in bats were reported from several European countries [7]. Thus far, lyssaviruses reported from Poland were characterized as EBLV-1 or BBLV [8].…”

Between roost contact is essential for maintenance of European bat lyssavirus type-2 in Myotis daubentonii bat reservoir: ‘The Swarming Hypothesis’

“…Fifteen cases of European bat lyssavirus type 2 (EBLV-2) have been detected in Daubenton's bats (Myotis daubentonii) in the UK, the first in 1996 and the most recent in 2017. Sero-surveillance has demonstrated a seroprevalence in the UK of up to 4% 14,[20][21][22] . Daubenton's bats are widespread temperate insectivorous bats with a range from Europe to Japan 23 .…”

Bokeloh bat lyssavirus isolation in a Natterer’s bat, Poland

“…Similarly, there are also large geographic distances between the German and French isolates within the different BBLV lineages A and B (Eggerbauer et al, ). This is different to EBLV‐2, where there is strong geographical clustering of lineages across Europe (McElhinney et al, ), although with such a small number of EBLV‐2 and BBLV cases reported such conclusions are considered preliminary.…”

“…In Europe, the vast majority of reported bat rabies cases have been characterized as European bat lyssavirus 1 (EBLV‐1), associated with Serotine bats ( Eptesicus serotinus , Eptesicus isabellinus ). European bat lyssavirus 2 (EBLV‐2) isolated mostly from Daubenton's bats ( Myotis daubentonii ) has also been reported in many European countries (McElhinney et al, ). In addition, single cases of rabies in bats have been reported: West Caucasian bat virus (WCBV) (Kuzmin, Hughes, Botvinkin, Orciari, & Rupprecht, ), Lleida bat lyssavirus (LLEBV) and Kotalahti bat lyssavirus (KBLV) (Aréchiga Ceballos et al, ; Nokireki, Tammiranta, Kokkonen, Kantala, & Gadd, ) in the West Caucasus, on the Iberian peninsula and Finland, respectively.…”