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dc.contributor.authorBeck, Jürgen
dc.contributor.authorSeitz, Stefan
dc.contributor.authorLauber, Chris
dc.contributor.authorNassal, Michael
dc.date.accessioned2021-05-07T09:49:10Z
dc.date.available2021-05-07T09:49:10Z
dc.date.issued2021-03-30
dc.identifier.citationProc Natl Acad Sci U S A. 2021 Mar 30;118(13):e2022373118. doi: 10.1073/pnas.2022373118.en_US
dc.identifier.pmid33753499
dc.identifier.doi10.1073/pnas.2022373118
dc.identifier.urihttp://hdl.handle.net/10033/622861
dc.description.abstractHepadnaviruses, with the human hepatitis B virus as prototype, are small, enveloped hepatotropic DNA viruses which replicate by reverse transcription of an RNA intermediate. Replication is initiated by a unique protein-priming mechanism whereby a hydroxy amino acid side chain of the terminal protein (TP) domain of the viral polymerase (P) is extended into a short DNA oligonucleotide, which subsequently serves as primer for first-strand synthesis. A key component in the priming of reverse transcription is the viral RNA element epsilon, which contains the replication origin and serves as a template for DNA primer synthesis. Here, we show that recently discovered non-enveloped fish viruses, termed nackednaviruses [C. Lauber et al., Cell Host Microbe 22, 387-399 (2017)], employ a fundamentally similar replication mechanism despite their huge phylogenetic distance and major differences in genome organization and viral lifestyle. In vitro cross-priming studies revealed that few strategic nucleotide substitutions in epsilon enable site-specific protein priming by heterologous P proteins, demonstrating that epsilon is functionally conserved since the two virus families diverged more than 400 Mya. In addition, other cis elements crucial for the hepadnavirus-typical replication of pregenomic RNA into relaxed circular double-stranded DNA were identified at conserved positions in the nackednavirus genomes. Hence, the replication mode of both hepadnaviruses and nackednaviruses was already established in their Paleozoic common ancestor, making it a truly ancient and evolutionary robust principle of genome replication that is more widespread than previously thought.en_US
dc.language.isoenen_US
dc.publisherAcademy of Sciencesen_US
dc.rightsAttribution 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectHBV long-term evolutionen_US
dc.subjectHBV replication mechanismen_US
dc.subjectinitiation of reverse transcriptionen_US
dc.subjectpaleovirologyen_US
dc.subjectprotein primingen_US
dc.titleConservation of the HBV RNA element epsilon in nackednaviruses reveals ancient origin of protein-primed reverse transcription.en_US
dc.typeArticleen_US
dc.identifier.eissn1091-6490
dc.contributor.departmentTWINCORE, Zentrum für experimentelle und klinische Infektionsforschung GmbH,Feodor-Lynen Str. 7, 30625 Hannover, Germany.en_US
dc.identifier.journalProceedings of the National Academy of Sciences of the United States of Americaen_US
dc.source.volume118
dc.source.issue13
dc.source.journaltitleProceedings of the National Academy of Sciences of the United States of America
dc.source.countryUnited States


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