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DOI10.1073/pnas.2022373118
Conservation of the HBV RNA element epsilon in nackednaviruses reveals ancient origin of protein-primed reverse transcription
Beck J.; Seitz S.; Lauber C.; Nassal M.
发表日期2021
ISSN00278424
卷号118期号:13
英文摘要Hepadnaviruses, 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. © 2021 National Academy of Sciences. All rights reserved.
英文关键词HBV long-term evolution; HBV replication mechanism; Initiation of reverse transcription; Paleovirology; Protein priming
语种英语
scopus关键词virus RNA; Article; controlled study; DNA virus; evolution; Hepatitis B virus; Nackednavirus; nonhuman; priority journal; reverse transcription; RNA structure; viral RNA element epsilon; virology; virus replication
来源期刊Proceedings of the National Academy of Sciences of the United States of America
文献类型期刊论文
条目标识符http://gcip.llas.ac.cn/handle/2XKMVOVA/180085
作者单位Medical Center–University of Freiburg, Department of Internal Medicine II/Molecular Biology, University of Freiburg, Freiburg, 79106, Germany; Department of Infectious Diseases, Molecular Virology, University of Heidelberg, Heidelberg, 69120, Germany; Division of Virus-Associated Carcinogenesis, German Cancer Research Center, Heidelberg, 69120, Germany; TWINCORE, Centre for Experimental and Clinical Infection Research, Institute for Experimental Infection Research, Hannover, 30625, Germany
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Beck J.,Seitz S.,Lauber C.,et al. Conservation of the HBV RNA element epsilon in nackednaviruses reveals ancient origin of protein-primed reverse transcription[J],2021,118(13).
APA Beck J.,Seitz S.,Lauber C.,&Nassal M..(2021).Conservation of the HBV RNA element epsilon in nackednaviruses reveals ancient origin of protein-primed reverse transcription.Proceedings of the National Academy of Sciences of the United States of America,118(13).
MLA Beck J.,et al."Conservation of the HBV RNA element epsilon in nackednaviruses reveals ancient origin of protein-primed reverse transcription".Proceedings of the National Academy of Sciences of the United States of America 118.13(2021).
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