Evolutionary analysis of whole-genome sequences confirms inter-farm transmission of Aleutian mink disease virus.

Aleutian mink disease virus (AMDV) is a frequently encountered pathogen associated with mink farming. Previous phylogenetic analyses of AMDV have been based on shorter and more conserved parts of the genome, e.g. the partial NS1 gene. Such fragments are suitable for detection but are less useful for elucidating transmission pathways while sequencing entire viral genomes provides additional informative sites and often results in better-resolved phylogenies. We explore how whole-genome sequencing can benefit investigations of AMDV transmission by reconstructing the relationships between AMDV field samples from a Danish outbreak. We show that whole-genome phylogenies are much better resolved than those based on the partial NS1 gene sequences extracted from the same alignment. Well-resolved phylogenies contain more information about the underlying transmission trees and are useful for understanding the spread of a pathogen. In the main case investigated here, the transmission path suggested by the tree structure was supported by epidemiological data. The use of molecular clock models further improved tree resolution and provided time estimates for the viral ancestors consistent with the proposed direction of spread. It was however impossible to infer transmission pathways from the partial NS1 gene tree, since all samples from the case farms branched out from a single internal node. A sliding window analysis showed that there were no shorter genomic regions providing the same phylogenetic resolution as the entire genome. Altogether, these results suggest that phylogenetic analyses based on whole-genome sequencing taking into account sampling dates and epidemiological data is a promising set of tools for clarifying AMDV transmission.