Genomic diversity and evolution of the lyssaviruses

Abstract

Lyssaviruses are RNA viruses with single-strand, negative-sense genomes responsible for rabies-like diseases in mammals. To date, genomic and evolutionary studies have most often utilized partial genome sequences, particularly of the nucleoprotein and glycoprotein genes, with little consideration of genome-scale evolution. Herein, we report the first genomic and evolutionary analysis using complete genome sequences of all recognised lyssavirus genotypes, including 14 new complete genomes of field isolates from 6 genotypes and one genotype that is completely sequenced for the first time. In doing so we significantly increase the extent of genome sequence data available for these important viruses. Our analysis of these genome sequence data reveals that all lyssaviruses have the same genomic organization. A phylogenetic analysis reveals strong geographical structuring, with the greatest genetic diversity in Africa, and an independent origin for the two known genotypes that infect European bats. We also suggest that multiple genotypes may exist within the diversity of viruses currently classified as 'Lagos Bat'. In sum, we show that rigorous phylogenetic techniques based on full length genome sequence provide the best discriminatory power for genotype classification within the lyssaviruses.

Figure 1. Schematic representation of lyssavirus genome organization and sequence similarity among 24 aligned genomes.

A. The 3′ leader, N-, P-, M-, G- and L-coding regions and the 5′ trailer region are shown. B. Sequence similarity is calculated by moving a window of 60 nucleotides along the aligned sequences. C. Sequence similarity is calculated by moving a window of 20 amino acids along the aligned sequences. Within each window, the similarity of any one position is taken to be the average of all the possible pairwise scores at that position and is calculated using PLOTCON (available at http://bioweb.pasteur.fr/seqanal/interfaces/plotcon.html).

Figure 2. Phylogenetic relationships of 22 complete coding regions of LYSSAV genomes representatives of the 7 genotypes.

The phylogeny was inferred using an ML procedure, and all horizontal branches are scaled according to the number of substitutions per site. Boot strap values (>95%) are shown for key nodes. The tree is mid-point rooted for purposes of clarity only.