Molecular Epidemiology of Terrestrial Rabies in the Former Soviet Union

Abstract

Fifty-five rabies virus isolates originating from different regions of the former Soviet Union (FSU) were compared with isolates originating from Eurasia, Africa, and North America according to complete or partial nucleoprotein (N) gene sequences. The FSU isolates formed five distinct groups. Group A represented viruses originating from the Arctic, which were similar to viruses from Alaska and Canada. Group B consisted of ''Arctic-like'' viruses, originating from the south of East Siberia and the Far East. Group C consisted of viruses circulating in the steppe and forest-steppe territories from the European part of Russia to Tuva and in Kazakhstan. These three phylogenetic groups were clearly different from the European cluster. Viruses of group D circulate near the western border of Russia. Their phylogenetic position is intermediate between group C and the European cluster. Group E consisted of viruses originating from the northwestern part of Russia and comprised a ''northeastern Europe'' group described earlier from the Baltic region. According to surveillance data, a specific host can be defined clearly only for group A (arctic fox; Alopex lagopus) and for the Far Eastern part of the group B distribution area (raccoon dog; Nyctereutes procyonoides). For other territories and rabies virus variants, the red fox (Vulpes vulpes) is the main virus reservoir. However, the steppe fox (Vulpes corsac), wolf (Canis lupus), and raccoon dog are also involved in virus circulation, depending on host population density. These molecular data, joined with surveillance information, demonstrate that the current fox rabies epizootic in the territory of the FSU developed independently of central and western Europe. No evidence of positive selection was found in the N genes of the isolates. In the glycoprotein gene, evidence of positive selection was strongly suggested in codons 156, 160, and 183. At these sites, no link between amino acid substitutions and phylogenetic placement or specific host species was detected.

Evolutionary timescale of rabies virus adaptation to North American bats inferred from the substitution rate of the nucleoprotein gene

“…Saturation of synonymous mutations (leading to potential underestimations of substitution rates; Holmes, 2003), recombination (reviewed by Awadalla, 2003), RNA secondary structure (Simmonds & Smith, 1999) and selection pressures can undoubtedly all contribute to misleading estimates of evolutionary rate. The lack of recombination found for complete bat N genes (Haydon et al, 2004), the fact that the RV genome is complexed with the N (Tordo & Kouknetzoff, 1993) and thus not subject to constraints on RNA secondary structure, and the strong evidence for purifying selection found in this study and elsewhere (Kissi et al, 1995;Holmes et al, 2002;Kuzmin et al, 2004) imply that the RV N gene is suitable for estimations of evolutionary rate and subsequent analysis of evolutionary history. Here, we assumed that the substitution rate of the RV N gene has remained constant over the course of the timescale measured (349-746 years).…”

“…This was no doubt due to the lack of positively selected codons along the N gene found here and elsewhere Kuzmin et al, 2004).…”

“…The lack of sustained spillover between RV variants (Smith, 2002;Krebs et al, 2002) ). This was no doubt due to the lack of positively selected codons along the N gene found here and elsewhere Kuzmin et al, 2004).…”

“…The lack of sustained spillover between RV variants (Smith, 2002;Krebs et al, 2002) ). This was no doubt due to the lack of positively selected codons along the N gene found here and elsewhere Kuzmin et al, 2004).Using complete bat RV variant N gene sequences, we have been able to reconstruct the evolutionary history of bat rabies in the Americas. Although the molecular clock model for the complete N gene alignment was rejected (probably in part due to both the amalgamation of RV variants with subtly different substitution rates and minor variation in m along the N gene), we have used the SRDT tree for evolutionary timescaling as we believe the mean m for this alignment to represent the best available approximation of substitution rate for the N gene.…”

Rabies virus strains circulating in Bhutan: implications for control

“…Many of these genes have been targeted for molecular studies. The N genes are highly conserved and have been extensively employed for rabies diagnosis using RT-PCR and other genetic analyses (Smith et al, 1992;Kuzmin et al, 2004;Denduangboripant et al, 2005;Bourhy et al, 2008). These studies have provided clearer understanding about the epidemiology of rabies virus distribution in the world.…”