Dokument-ID Dokumenttyp Autoren/innen Persönliche Herausgeber/innen Haupttitel Abstract Auflage Verlagsort Verlag Herausgeber (Institution) Erscheinungsjahr Titel des übergeordneten Werkes Jahrgang/Band ISBN Veranstaltung Veranstaltungsort Beginndatum der Veranstaltung Enddatum der Veranstaltung Ausgabe/Heft Erste Seite Letzte Seite URN DOI Lizenz Datum der Freischaltung OPUS4-42905 Zeitschriftenartikel Trimpert, J.; Groenke, N.; Jenckel, M.; He, Shulin; Kunec, D.; Szpara, M.L.; Spatz, S.J.; Osterrieder, N.; McMahon, Dino Peter A phylogenomic analysis of Marek's disease virus (MDV) reveals independent paths to virulence in Eurasia and North America Virulence determines the impact a pathogen has on the fitness of its host, yet current understanding of the evolutionary origins and causes of virulence of many pathogens is surprisingly incomplete. Here, we explore the evolution of Marek's disease virus (MDV), a herpesvirus commonly afflicting chickens and rarely other avian species. The history of MDV in the 20th century represents an important case study in the evolution of virulence. The severity of MDV infection in chickens has been rising steadily since the adoption of intensive farming techniques and vaccination programs in the 1950s and 1970s, respectively. It has remained uncertain, however, which of these factors is causally more responsible for the observed increase in virulence of circulating viruses. We conducted a phylogenomic study to understand the evolution of MDV in the context of dramatic changes to poultry farming and disease control. Our analysis reveals evidence of geographical structuring of MDV strains, with reconstructions supporting the emergence of virulent viruses independently in North America and Eurasia. Of note, the emergence of virulent viruses appears to coincide approximately with the introduction of comprehensive vaccination on both continents. The time-dated phylogeny also indicated that MDV has a mean evolutionary rate of ~1.6 × 10−5 substitutions per site per year. An examination of gene-linked mutations did not identify a strong association between mutational variation and virulence phenotypes, indicating that MDV may evolve readily and rapidly under strong selective pressures and that multiple genotypic pathways may underlie virulence adaptation in MDV. John Wiley & Sons Ltd. 2017 Evolutionary Applications 10 10 1091 1101 urn:nbn:de:kobv:b43-429054 10.1111/eva.12515 http://creativecommons.org/licenses/by/3.0/de/deed.de 2017-11-15 OPUS4-48896 Zeitschriftenartikel Trimpert, J.; Groenke, N.; Kunec, D.; Eschke, K.; He, Shulin; McMahon, Dino Peter; Osterrieder, N. A proofreading-impaired herpesvirus generates populations with quasispecies-like structure RNA virus populations are composed of highly diverse individuals that form a cloud of related sequences commonly referred to as a 'quasispecies'1-3. This diversity arises as a consequence of low-fidelity genome replication4,5. By contrast, DNA Virus populations contain more uniform individuals with similar fitness6. Genome diversity is often correlated with increased Fitness in RNA viruses, while DNA viruses are thought to require more faithful genome replication. During DNA replication, erroneously incorporated bases are removed by a 3′-5′ exonuclease, a highly conserved enzymatic function of replicative DNA but not RNA polymerases. This proofreading process enhances replication fidelity and ensures the genome integrity of DNA organisms, including large DNA viruses7. Here, we show that a herpesvirus can tolerate impaired exonucleolytic proofreading, resulting in DNA virus populations, which, as in RNA viruses8, are composed of highly diverse genotypes of variable individual fitness. This indicates that herpesvirus mutant diversity may compensate for individual Fitness loss. Notably, in vivo infection with diverse virus populations results in a marked increase in virulence compared to genetically homogenous parental virus. While we cannot exclude that the increase in virulence is caused by selection of and/or interactions between individual genotypes, our findings are consistent with quasispecies dynamics. Our results contrast with traditional views of DNA virus replication and evolution, and indicate that a substantial increase in population diversity can lead to higher virulence. London Nature Publishing Group 2019 Nature Microbiology 4 2175 2183 10.1038/s41564-019-0547-x 2019-09-10