Pathogen evolution and disease emergence in carnivores

Abstract

Emerging infectious diseases constitute some of the most pressing problems for both human and domestic animal health, and biodiversity conservation. Currently it is not clear whether the removal of past constraints on geographical distribution and transmission possibilities for pathogens alone are sufficient to give rise to novel host-pathogen combinations, or whether pathogen evolution is also generally required for establishment in novel hosts. Canine distemper virus (CDV) is a morbillivirus that is prevalent in the world dog population and poses an important conservation threat to a diverse range of carnivores. We performed an extensive phylogenetic and molecular evolution analysis on complete sequences of all CDV genes to assess the role of selection and recombination in shaping viral genetic diversity and driving the emergence of CDV in non-dog hosts. We tested the specific hypothesis that molecular adaptation at known receptor-binding sites of the haemagglutinin gene is associated with independent instances of the spread of CDV to novel non-dog hosts in the wild. This hypothesis was upheld, providing compelling evidence that repeated evolution at known functional sites (in this case residues 530 and 549 of the haemagglutinin molecule) is associated with multiple independent occurrences of disease emergence in a range of novel host species.

Figure 1

Phylogenetic relationship between CDV strains based on H gene sequences and the distribution of H protein residues at sites under positive selection across lineages. PDV-1 strains were used as out-group and only the tree topology is shown for clarity. Bayesian posterior probabilities and maximum likelihood bootstrap support values (in parentheses) for the major lineages are given at the nodes. Host species, accession number and isolate location are also shown. CDV strains form seven distinct clusters: America-1 (vaccines), America-2, Arctic-Like, Asia-1, Asia-2, Europe and European wildlife. Residues 530 and 549 are located in the regions of SLAM receptor-binding importance. Circled residues are substitutions at residues 530 and 549 of isolates from non-dog hosts.

Figure 2

CDV H protein predicted tertiary structure (von Messling et al. 2005). Residues 527, 528, 529 and 552 (required for SLAM-dependent fusion and conserved between all morbilliviruses), as well residues 526, 547 and 548 (also important in SLAM-dependent fusion), are shown in black. Residues under the influence of positive selection are shown in grey. (a) Top view. (b) Side view. The illustrations of the models were prepared with Pymol (DeLano 2002).