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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.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.zeige mehrzeige weniger

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Metadaten
Autoren/innen:J. Trimpert, N. Groenke, D. Kunec, K. Eschke, Shulin He, Dino Peter McMahon, N. Osterrieder
Dokumenttyp:Zeitschriftenartikel
Veröffentlichungsform:Verlagsliteratur
Sprache:Englisch
Titel des übergeordneten Werkes (Englisch):Nature Microbiology
Jahr der Erstveröffentlichung:2019
Organisationseinheit der BAM:4 Material und Umwelt
4 Material und Umwelt / 4.1 Biologische Materialschädigung und Referenzorganismen
4 Material und Umwelt / 4.0 Abteilungsleitung und andere
Verlag:Nature Publishing Group
Verlagsort:London
Jahrgang/Band:4
Erste Seite:2175
Letzte Seite:2183
DDC-Klassifikation:Technik, Medizin, angewandte Wissenschaften / Ingenieurwissenschaften / Sanitär- und Kommunaltechnik; Umwelttechnik
Freie Schlagwörter:Evolution; Marek's virus; Quasispecies; Virulence
Themenfelder/Aktivitätsfelder der BAM:Umwelt
Umwelt / Umweltschadstoffe
DOI:https://doi.org/10.1038/s41564-019-0547-x
URL:http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=Alerting&SrcApp=Alerting&DestApp=MEDLINE&DestLinkType=FullRecord&UT=MEDLINE:31477893
ISSN:2058-5276
Zugehöriger Identifikator:https://doi.org/10.1038/s41564-019-0598-z
Bemerkung:
Corrigendum: Nature Microbiology 4 (2019) 2025
Verfügbarkeit des Dokuments:Datei im Netzwerk der BAM verfügbar ("Closed Access")
Datum der Freischaltung:10.09.2019
Referierte Publikation:Ja
Datum der Eintragung als referierte Publikation:10.09.2019