Abstract
Theoretically, homogeneous environments favor the evolution of specialists whereas heterogeneous environments favor generalists. Canine distemper is a multi-host carnivore disease caused by canine distemper virus (CDV). The described cell receptor of CDV is SLAM (CD150). Attachment of CDV hemagglutinin protein (CDV-H) to this receptor facilitates fusion and virus entry in cooperation with the fusion protein (CDV-F). We investigated whether CDV strains co-evolved in the large, homogeneous domestic dog population exhibited specialist traits, and strains adapted to the heterogeneous environment of smaller populations of different carnivores exhibited generalist traits. Comparison of amino acid sequences of the SLAM binding region revealed higher similarity between sequences from Canidae species than to sequences from other carnivore families. Using an in vitro assay, we quantified syncytia formation mediated by CDV-H proteins from dog and non-dog CDV strains in cells expressing dog, lion or cat SLAM. CDV-H proteins from dog strains produced significantly higher values with cells expressing dog SLAM than with cells expressing lion or cat SLAM. CDV-H proteins from strains of non-dog species produced similar values in all three cell types, but lower values in cells expressing dog SLAM than the values obtained for CDV-H proteins from dog strains. By experimentally changing one amino acid (Y549H) in the CDV-H protein of one dog strain we decreased expression of specialist traits and increased expression of generalist traits, thereby confirming its functional importance. A virus titer assay demonstrated that dog strains produced higher titers in cells expressing dog SLAM than cells expressing SLAM of non-dog hosts, which suggested possible fitness benefits of specialization post-cell entry. We provide in vitro evidence for the expression of specialist and generalist traits by CDV strains, and fitness trade-offs across carnivore host environments caused by antagonistic pleiotropy. These findings extend knowledge on CDV molecular epidemiology of particular relevance to wild carnivores.
Highlights
Theoretical [1,2,3] and empirical evidence [4,5,6,7,8,9] suggests that organisms evolving in homogeneous environments tend to be more specialized than those evolving in heterogeneous environments
We predicted that experimental substitution of residue Y, characteristic of domestic dog canine distemper virus (CDV) strains at site 549, with residue H, typical for CDV strains from non-dog hosts [46,49], in the CDV hemagglutinin protein (CDV-H) protein from one domestic dog strain would decrease expression of specialist traits in the syncytia formation assay, which is what our results showed
This study presents evidence consistent with the idea that strong co-evolution of CDV strains in the globally large, homogeneous domestic dog population favored CDV-H proteins specialized to bind to SLAM (CD150) cell receptors of domestic dogs, whereas weak co-evolution in the heterogeneous environment of different carnivore species favored generalist strains less well adapted to domestic dog receptors but able to bind to this cell receptor in a broad range of carnivore species
Summary
Theoretical [1,2,3] and empirical evidence [4,5,6,7,8,9] suggests that organisms evolving in homogeneous environments tend to be more specialized than those evolving in heterogeneous environments. The CDV-H protein-host SLAM binding mechanism provides a useful cellular system to test whether stronger co-evolution between CDV and its most abundant host has produced strains that exhibit specialist traits in the globally large domestic dog population that persists at high densities in many human altered habitats [50], and generalist traits in CDV strains in other carnivore species in habitats containing several potential wildlife hosts and few or no domestic dogs [30,31,51] This idea is plausible, given the presence of genetically distinct wildlife lineages of CDV, most notably in non-canid species in Europe [49,52,53] and genetic differences between CDV strains in domestic dogs and wild carnivores in relation to the residue at site 549 in the CDV-H protein [46,49], but to our knowledge has not been tested. We predicted that experimental substitution of residue Y, characteristic of domestic dog CDV strains at site 549, with residue H, typical for CDV strains from non-dog hosts [46,49], in the CDV-H protein from one domestic dog strain would decrease expression of specialist traits in the syncytia formation assay, which is what our results showed
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
