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J Virol. 2019 Oct 16. pii: JVI.01162-19. doi: 10.1128/JVI.01162-19. [Epub ahead of print]

Limited intra-host diversity and background evolution accompany 40 years of canine parvovirus host adaptation and spread.

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Baker Institute for Animal Health, Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
Department of Biochemistry and Molecular Biology, USA Millennium Science Complex, University Park, PA 16802, USA.
Department of Comparative, Diagnostic, and Population Medicine, College of Veterinary Medicine, University of Florida, 2015 SW 16th Ave, Gainesville, FL 32610, USA.
Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
Dept. of Veterinary Medicine, University of Ibadan, Ibadan, Nigeria.
Huck Institutes of the Life Sciences, The Pennsylvania State University, University Park, PA 16802, USA.
Department of Medicine, College of Medicine, The Pennsylvania State University, Hershey, Pennsylvania, USA.
Marie Bashir Institute for Infectious Diseases and Biosecurity, Charles Perkins Centre, School of Life & Environmental Sciences and Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia.
Baker Institute for Animal Health, Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.


Canine parvovirus (CPV) is a highly successful pathogen that has sustained pandemic circulation in dogs for more than 40 years. Here, integrating full-genome and deep sequencing analyses, structural information, and in vitro experimentation, we describe the macro- and micro-scale features that accompany CPV's evolutionary success. Despite 40 years of viral evolution, all CPV variants are more than ∼99% identical in nucleotide sequence, with only a limited number (<40) of substitutions becoming fixed or widespread during this time. Notably, most substitutions in the major capsid protein (VP2) gene are nonsynonymous, altering amino acid residues that fall within, or adjacent to, the overlapping receptor footprint or antigenic regions, suggesting that natural selection has channeled much of CPV evolution. Among the limited number of variable sites, CPV genomes exhibit complex patterns of variation that include parallel evolution, reversion, and recombination, compromising phylogenetic inference. At the intra-host level, deep sequencing of viral DNA in original clinical samples from dogs and other host species sampled between 1978 and 2018 revealed few sub-consensus single nucleotide variants (SNVs) above ∼0.5%, and experimental passages demonstrate that substantial pre-existing genetic variation is not necessarily required for rapid host receptor driven adaptation. Together, these findings suggest that although CPV is capable of rapid host adaptation, a relatively low mutation rate, pleiotropy, and/or a lack of selective challenges since its initial emergence have inhibited the long-term accumulation of genetic diversity. Hence, continuously high levels of inter- and intra-host diversity are not necessarily required for virus host adaptation.IMPORTANCE Rapid mutation rates and correspondingly high levels of intra- and inter-host diversity are often cited as key features of viruses with the capacity for emergence and sustained transmission in a new host species. However, most of this information comes from studies of RNA viruses, with relatively little known about evolutionary processes in viruses with single-stranded DNA (ssDNA) genomes. Here we provide a unique model of virus evolution, integrating both long-term global-scale and short-term intra-host evolutionary processes of a ssDNA virus that emerged to cause a pandemic in a new host animal. Our analysis reveals that successful host jumping and sustained onward transmission does not necessarily depend on a high level of intra-host diversity nor result in the continued accumulation of high levels of long-term evolution change. These findings indicate that all aspects of the biology and ecology of a virus are relevant when considering their adaptability.


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