Genetic diversity accelerates canine distemper virus adaptation to ferrets

RNA viruses adapt rapidly to new host environments by generating highly diverse genome sets, so-called “quasispecies”. Minor genetic variants promote their rapid adaptation allowing for emergence of drug-resistance or immune-escape mutants. Understanding these adaptation processes is highly relevant to assess the risk of cross-species transmission, and safety and efficacy of vaccines and antivirals. We hypothesized that genetic memory within a viral genome population facilitates rapid adaptation. We investigated the adaptation of the Morbillivirus canine distemper virus (CDV) to ferrets and compared an attenuated, Vero cell-adapted virus isolate (5804) with its recombinant derivative (r5804) over consecutive in vivo passages in ferrets. We performed RNA-seq analyses of infected organ homogenates and determined the mutant spectra within the CDV genome populations replicating in these tissues at each passage.