Antigenic and molecular characterization of bat rabies virus in Europe

Abstract

The predominant role of Eptesicus serotinus in the epizootic of bat rabies in Europe was further outlined by the first isolation of the rabies virus from this species in France. The distribution of the virus was studied in naturally infected E. serotinus bats at the time of death and suggested that the papillae of the tongue and the respiratory mucosa may play a role in virus production and excretion. The analysis of 501 French rabies virus isolates from various animal species by antinucleocapsid monoclonal antibodies indicated that transmission of the disease from bats to terrestrial animals is unlikely. The antigenic profile of two isolates from French bats corresponded to that of European bat lyssavirus type 1 (EBL1). Comparisons of 12 different isolates from bats with antinucleocapsid and antiglycoprotein monoclonal antibodies and by direct sequencing of the polymerase chain reaction amplification product of the N gene indicated that EBL1, EBL2, Duvenhage virus (serotype 4 of lyssavirus), and the European fox rabies virus (serotype 1) are phylogenetically distant. They formed four tight genetic clusters named genotypes. EBL1 was shown to be antigenically and genetically more closely related to Duvenhage virus than to EBL2. We propose that EBL1 and EBL2 constitute two distinct genotypes which further serologic characterization will probably classify as new serotypes. We also report a simple method for the rapid characterization of EBL based on the digestion of the polymerase chain reaction product of the N gene by three restriction endonucleases.

European bat lyssaviruses: Distribution, prevalence and implications for conservation

“…The presence of EBLVs in Europe was first documented in 1954 (Kappelar, 1989;King et al, 2004), and during the period 1977-2004, 783 EBLV confirmed cases (by isolation of viral RNA) have been reported (King et al, 2004;Mü ller, 2000;Rabies Bulletin Europe, 2001, 2003. EBLV-1 (genotype 5) and EBLV-2 (genotype 6) are related to, but can be genetically and antigenically distinguished from classical rabies (RABV: genotype 1) (Bourhy et al, 1992(Bourhy et al, , 1993(Bourhy et al, , 1999Badrane et al, 2001). In addition, both EBLVs can be distinguished from each other using sequence analysis of the N and/or G genes (Fooks et al, 2003a).…”

“…Active infection (replicating virus in the CNS and/or excretion of virus in saliva) caused by EBLV-1 has not been recorded in the UK to date, and the disparity between EBLV-1 records in Europe and the UK may be related to the limited geographical distribution and population size of E. serotinus within the UK. Spillover of EBLV-1 (Table 6) into sheep has occurred on two separate occasions in Denmark, in 1998(Ronsholt, 2002Tjørnehøj et al, 2006), and into a stone marten in Germany (Mü ller et al, 2001), a domestic cat (antibodies only) in Denmark (Tjørnehøj et al, 2004) and one confirmed human case (Selimov et al, 1989;Bourhy et al, 1992). A further two unconfirmed human cases of suspected bat origin have also been reported (Table 6) (Rabies Bulletin Europe, 1986;Botvinkin et al, 2006).…”

Status of antiviral therapeutics against rabies virus and related emerging lyssaviruses

“…Advances in molecular biology and a better understanding of RABV pathogenesis have led to new approaches to address the problem. Of all options, we consider the RABV polymerase complex to represent the most promising target for direct-acting antivirals due to the comparably low conservation of G across lyssaviruses [12,17,158,174,[189][190][191][192]. The heterologous polymerase complex offers druggable protein-protein interfaces, essential enzymatic centers, and opportunity for allosteric and competitive substrate-analog inhibitors.…”

“…Monoclonal antibodies (mAbs) targeting RABV G have proven antiviral efficacy [15,[152][153][154]. Broad panels of antibodies against rabies G revealed primary clusters for antibody recognition in distinct regions of the G ectodomain [18,[155][156][157][158]. As shown in figure 5, these antigenic sites (AS) include ASI (a.a. 226-231), ASII (a.a. [34][35][36][37][38][39][40][41][42], ASIII (a.a.330-338), ASIV (a.a. 251), ASV (a.a. 261-264), and ASVI (a.a. 264).…”

The other rabies viruses: The emergence and importance of lyssaviruses from bats and other vertebrates

“…Indeed, EBLV-1 is antigenically and genetically more closely related to Duvenhage virus than it is to EBLV-2. 26 EBLV-2 was isolated from a zoologist who died in Finland with what was diagnosed as rabies. 27 Similar viruses were isolated from pond bats (Myotis dasycneme) in The Netherlands.…”